Skip to main content
Erschienen in: Cancer and Metastasis Reviews 4/2016

02.12.2016

Immunotherapy for breast cancer: past, present, and future

verfasst von: Alison Spellman, Shou-Ching Tang

Erschienen in: Cancer and Metastasis Reviews | Ausgabe 4/2016

Einloggen, um Zugang zu erhalten

Abstract

Immunotherapy has shown promise in many solid tumors including melanoma and non-small cell lung cancer with an evolving role in breast cancer. Immunotherapy encompasses a wide range of therapies including immune checkpoint inhibition, monoclonal antibodies, bispecific antibodies, vaccinations, antibody-drug conjugates, and identifying other emerging interventions targeting the tumor microenvironment. Increasing efficacy of these treatments in breast cancer patients requires identification of better biomarkers to guide patient selection; recognizing when to initiate these therapies in multi-modality treatment plans; establishing novel assays to monitor immune-mediated responses; and creating combined systemic therapy options incorporating conventional treatments such as chemotherapy and endocrine therapy. This review will focus on the current role and future directions of many of these immunotherapies in breast cancer, as well as highlighting clinical trials that are investigating several of these active issues.
Literatur
3.
Zurück zum Zitat Fisher, R. I., Rosenberg, S. A., & Fyfe, G. (2000). Long-term survival update for high-dose recombinant interleukin-2 in patients with renal cell carcinoma. The Cancer Journal from Scientific American, 6(Suppl 1), S55–S57.PubMed Fisher, R. I., Rosenberg, S. A., & Fyfe, G. (2000). Long-term survival update for high-dose recombinant interleukin-2 in patients with renal cell carcinoma. The Cancer Journal from Scientific American, 6(Suppl 1), S55–S57.PubMed
4.
Zurück zum Zitat Eggermont, A. M., Suciu, S., Santinami, M., Testori, A., Kruit, W. H., Marsden, J., et al. (2008). Adjuvant therapy with pegylated interferon alfa-2b versus observation alone in resected stage III melanoma: final results of EORTC 18991, a randomised phase III trial. Lancet, 372(9633), 117–126. doi:10.1016/S0140-6736(08)61033-8.PubMedCrossRef Eggermont, A. M., Suciu, S., Santinami, M., Testori, A., Kruit, W. H., Marsden, J., et al. (2008). Adjuvant therapy with pegylated interferon alfa-2b versus observation alone in resected stage III melanoma: final results of EORTC 18991, a randomised phase III trial. Lancet, 372(9633), 117–126. doi:10.​1016/​S0140-6736(08)61033-8.PubMedCrossRef
5.
Zurück zum Zitat Fyfe, G., Fisher, R. I., Rosenberg, S. A., Sznol, M., Parkinson, D. R., & Louie, A. C. (1995). Results of treatment of 255 patients with metastatic renal cell carcinoma who received high-dose recombinant interleukin-2 therapy. Journal of Clinical Oncology, 13(3), 688–696.PubMed Fyfe, G., Fisher, R. I., Rosenberg, S. A., Sznol, M., Parkinson, D. R., & Louie, A. C. (1995). Results of treatment of 255 patients with metastatic renal cell carcinoma who received high-dose recombinant interleukin-2 therapy. Journal of Clinical Oncology, 13(3), 688–696.PubMed
6.
Zurück zum Zitat Chavez-Galan, L., Arenas-Del Angel, M. C., Zenteno, E., Chavez, R., & Lascurain, R. (2009). Cell death mechanisms induced by cytotoxic lymphocytes. Cellular & Molecular Immunology, 6(1), 15–25. doi:10.1038/cmi.2009.3.CrossRef Chavez-Galan, L., Arenas-Del Angel, M. C., Zenteno, E., Chavez, R., & Lascurain, R. (2009). Cell death mechanisms induced by cytotoxic lymphocytes. Cellular & Molecular Immunology, 6(1), 15–25. doi:10.​1038/​cmi.​2009.​3.CrossRef
8.
9.
Zurück zum Zitat Chung, S., Lin, Y. L., Reed, C., Ng, C., Cheng, Z. J., Malavasi, F., et al. (2014). Characterization of in vitro antibody-dependent cell-mediated cytotoxicity activity of therapeutic antibodies - impact of effector cells. Journal of Immunological Methods, 407, 63–75. doi:10.1016/j.jim.2014.03.021.PubMedCrossRef Chung, S., Lin, Y. L., Reed, C., Ng, C., Cheng, Z. J., Malavasi, F., et al. (2014). Characterization of in vitro antibody-dependent cell-mediated cytotoxicity activity of therapeutic antibodies - impact of effector cells. Journal of Immunological Methods, 407, 63–75. doi:10.​1016/​j.​jim.​2014.​03.​021.PubMedCrossRef
13.
Zurück zum Zitat Peggs, K. S., Quezada, S. A., Chambers, C. A., Korman, A. J., & Allison, J. P. (2009). Blockade of CTLA-4 on both effector and regulatory T cell compartments contributes to the antitumor activity of anti-CTLA-4 antibodies. The Journal of Experimental Medicine, 206(8), 1717–1725. doi:10.1084/jem.20082492.PubMedPubMedCentralCrossRef Peggs, K. S., Quezada, S. A., Chambers, C. A., Korman, A. J., & Allison, J. P. (2009). Blockade of CTLA-4 on both effector and regulatory T cell compartments contributes to the antitumor activity of anti-CTLA-4 antibodies. The Journal of Experimental Medicine, 206(8), 1717–1725. doi:10.​1084/​jem.​20082492.PubMedPubMedCentralCrossRef
14.
15.
Zurück zum Zitat Simpson, T. R., Li, F., Montalvo-Ortiz, W., Sepulveda, M. A., Bergerhoff, K., Arce, F., et al. (2013). Fc-dependent depletion of tumor-infiltrating regulatory T cells co-defines the efficacy of anti-CTLA-4 therapy against melanoma. The Journal of Experimental Medicine, 210(9), 1695–1710. doi:10.1084/jem.20130579.PubMedPubMedCentralCrossRef Simpson, T. R., Li, F., Montalvo-Ortiz, W., Sepulveda, M. A., Bergerhoff, K., Arce, F., et al. (2013). Fc-dependent depletion of tumor-infiltrating regulatory T cells co-defines the efficacy of anti-CTLA-4 therapy against melanoma. The Journal of Experimental Medicine, 210(9), 1695–1710. doi:10.​1084/​jem.​20130579.PubMedPubMedCentralCrossRef
16.
Zurück zum Zitat Bulliard, Y., Jolicoeur, R., Windman, M., Rue, S. M., Ettenberg, S., Knee, D. A., et al. (2013). Activating Fc gamma receptors contribute to the antitumor activities of immunoregulatory receptor-targeting antibodies. The Journal of Experimental Medicine, 210(9), 1685–1693. doi:10.1084/jem.20130573.PubMedPubMedCentralCrossRef Bulliard, Y., Jolicoeur, R., Windman, M., Rue, S. M., Ettenberg, S., Knee, D. A., et al. (2013). Activating Fc gamma receptors contribute to the antitumor activities of immunoregulatory receptor-targeting antibodies. The Journal of Experimental Medicine, 210(9), 1685–1693. doi:10.​1084/​jem.​20130573.PubMedPubMedCentralCrossRef
17.
Zurück zum Zitat Ribas, A., Kefford, R., Marshall, M. A., Punt, C. J., Haanen, J. B., Marmol, M., et al. (2013). Phase III randomized clinical trial comparing tremelimumab with standard-of-care chemotherapy in patients with advanced melanoma. Journal of Clinical Oncology, 31(5), 616–622. doi:10.1200/JCO.2012.44.6112.PubMedPubMedCentralCrossRef Ribas, A., Kefford, R., Marshall, M. A., Punt, C. J., Haanen, J. B., Marmol, M., et al. (2013). Phase III randomized clinical trial comparing tremelimumab with standard-of-care chemotherapy in patients with advanced melanoma. Journal of Clinical Oncology, 31(5), 616–622. doi:10.​1200/​JCO.​2012.​44.​6112.PubMedPubMedCentralCrossRef
18.
Zurück zum Zitat Vonderheide, R. H., LoRusso, P. M., Khalil, M., Gartner, E. M., Khaira, D., Soulieres, D., et al. (2010). Tremelimumab in combination with exemestane in patients with advanced breast cancer and treatment-associated modulation of inducible costimulator expression on patient T cells. Clinical Cancer Research, 16(13), 3485–3494. doi:10.1158/1078-0432.CCR-10-0505.PubMedCrossRef Vonderheide, R. H., LoRusso, P. M., Khalil, M., Gartner, E. M., Khaira, D., Soulieres, D., et al. (2010). Tremelimumab in combination with exemestane in patients with advanced breast cancer and treatment-associated modulation of inducible costimulator expression on patient T cells. Clinical Cancer Research, 16(13), 3485–3494. doi:10.​1158/​1078-0432.​CCR-10-0505.PubMedCrossRef
20.
Zurück zum Zitat Fife, B. T., Pauken, K. E., Eagar, T. N., Obu, T., Wu, J., Tang, Q., et al. (2009). Interactions between PD-1 and PD-L1 promote tolerance by blocking the TCR-induced stop signal. Nature Immunology, 10(11), 1185–1192. doi:10.1038/ni.1790.PubMedPubMedCentralCrossRef Fife, B. T., Pauken, K. E., Eagar, T. N., Obu, T., Wu, J., Tang, Q., et al. (2009). Interactions between PD-1 and PD-L1 promote tolerance by blocking the TCR-induced stop signal. Nature Immunology, 10(11), 1185–1192. doi:10.​1038/​ni.​1790.PubMedPubMedCentralCrossRef
21.
Zurück zum Zitat Barber, D. L., Wherry, E. J., Masopust, D., Zhu, B., Allison, J. P., Sharpe, A. H., et al. (2006). Restoring function in exhausted CD8 T cells during chronic viral infection. Nature, 439(7077), 682–687. doi:10.1038/nature04444.PubMedCrossRef Barber, D. L., Wherry, E. J., Masopust, D., Zhu, B., Allison, J. P., Sharpe, A. H., et al. (2006). Restoring function in exhausted CD8 T cells during chronic viral infection. Nature, 439(7077), 682–687. doi:10.​1038/​nature04444.PubMedCrossRef
22.
Zurück zum Zitat Freeman, G. J., Long, A. J., Iwai, Y., Bourque, K., Chernova, T., Nishimura, H., et al. (2000). Engagement of the PD-1 immunoinhibitory receptor by a novel B7 family member leads to negative regulation of lymphocyte activation. The Journal of Experimental Medicine, 192(7), 1027–1034.PubMedPubMedCentralCrossRef Freeman, G. J., Long, A. J., Iwai, Y., Bourque, K., Chernova, T., Nishimura, H., et al. (2000). Engagement of the PD-1 immunoinhibitory receptor by a novel B7 family member leads to negative regulation of lymphocyte activation. The Journal of Experimental Medicine, 192(7), 1027–1034.PubMedPubMedCentralCrossRef
23.
24.
Zurück zum Zitat Dong, H., Strome, S. E., Salomao, D. R., Tamura, H., Hirano, F., Flies, D. B., et al. (2002). Tumor-associated B7-H1 promotes T-cell apoptosis: a potential mechanism of immune evasion. Nature Medicine, 8(8), 793–800. doi:10.1038/nm730.PubMed Dong, H., Strome, S. E., Salomao, D. R., Tamura, H., Hirano, F., Flies, D. B., et al. (2002). Tumor-associated B7-H1 promotes T-cell apoptosis: a potential mechanism of immune evasion. Nature Medicine, 8(8), 793–800. doi:10.​1038/​nm730.PubMed
25.
Zurück zum Zitat Taube, J. M., Anders, R. A., Young, G. D., Xu, H., Sharma, R., McMiller, T. L., et al. (2012). Colocalization of inflammatory response with B7-h1 expression in human melanocytic lesions supports an adaptive resistance mechanism of immune escape. Science Translational Medicine, 4(127), 127ra137. doi:10.1126/scitranslmed.3003689.CrossRef Taube, J. M., Anders, R. A., Young, G. D., Xu, H., Sharma, R., McMiller, T. L., et al. (2012). Colocalization of inflammatory response with B7-h1 expression in human melanocytic lesions supports an adaptive resistance mechanism of immune escape. Science Translational Medicine, 4(127), 127ra137. doi:10.​1126/​scitranslmed.​3003689.CrossRef
26.
Zurück zum Zitat Muenst, S., Soysal, S. D., Gao, F., Obermann, E. C., Oertli, D., & Gillanders, W. E. (2013). The presence of programmed death 1 (PD-1)-positive tumor-infiltrating lymphocytes is associated with poor prognosis in human breast cancer. Breast Cancer Research and Treatment, 139(3), 667–676. doi:10.1007/s10549-013-2581-3.PubMedCrossRef Muenst, S., Soysal, S. D., Gao, F., Obermann, E. C., Oertli, D., & Gillanders, W. E. (2013). The presence of programmed death 1 (PD-1)-positive tumor-infiltrating lymphocytes is associated with poor prognosis in human breast cancer. Breast Cancer Research and Treatment, 139(3), 667–676. doi:10.​1007/​s10549-013-2581-3.PubMedCrossRef
27.
Zurück zum Zitat Ghebeh, H., Mohammed, S., Al-Omair, A., Qattan, A., Lehe, C., Al-Qudaihi, G., et al. (2006). The B7-H1 (PD-L1) T lymphocyte-inhibitory molecule is expressed in breast cancer patients with infiltrating ductal carcinoma: correlation with important high-risk prognostic factors. Neoplasia, 8(3), 190–198. doi:10.1593/neo.05733.PubMedPubMedCentralCrossRef Ghebeh, H., Mohammed, S., Al-Omair, A., Qattan, A., Lehe, C., Al-Qudaihi, G., et al. (2006). The B7-H1 (PD-L1) T lymphocyte-inhibitory molecule is expressed in breast cancer patients with infiltrating ductal carcinoma: correlation with important high-risk prognostic factors. Neoplasia, 8(3), 190–198. doi:10.​1593/​neo.​05733.PubMedPubMedCentralCrossRef
28.
Zurück zum Zitat Sabatier, R., Finetti, P., Mamessier, E., Adelaide, J., Chaffanet, M., Ali, H. R., et al. (2015). Prognostic and predictive value of PDL1 expression in breast cancer. Oncotarget, 6(7), 5449–5464.PubMedCrossRef Sabatier, R., Finetti, P., Mamessier, E., Adelaide, J., Chaffanet, M., Ali, H. R., et al. (2015). Prognostic and predictive value of PDL1 expression in breast cancer. Oncotarget, 6(7), 5449–5464.PubMedCrossRef
30.
Zurück zum Zitat Gatalica, Z., Snyder, C., Maney, T., Ghazalpour, A., Holterman, D. A., Xiao, N., et al. (2014). Programmed cell death 1 (PD-1) and its ligand (PD-L1) in common cancers and their correlation with molecular cancer type. Cancer Epidemiology, Biomarkers & Prevention, 23(12), 2965–2970. doi:10.1158/1055-9965.EPI-14-0654.CrossRef Gatalica, Z., Snyder, C., Maney, T., Ghazalpour, A., Holterman, D. A., Xiao, N., et al. (2014). Programmed cell death 1 (PD-1) and its ligand (PD-L1) in common cancers and their correlation with molecular cancer type. Cancer Epidemiology, Biomarkers & Prevention, 23(12), 2965–2970. doi:10.​1158/​1055-9965.​EPI-14-0654.CrossRef
31.
Zurück zum Zitat Zhang, P., Su, D. M., Liang, M., & Fu, J. (2008). Chemopreventive agents induce programmed death-1-ligand 1 (PD-L1) surface expression in breast cancer cells and promote PD-L1-mediated T cell apoptosis. Molecular Immunology, 45(5), 1470–1476. doi:10.1016/j.molimm.2007.08.013.PubMedCrossRef Zhang, P., Su, D. M., Liang, M., & Fu, J. (2008). Chemopreventive agents induce programmed death-1-ligand 1 (PD-L1) surface expression in breast cancer cells and promote PD-L1-mediated T cell apoptosis. Molecular Immunology, 45(5), 1470–1476. doi:10.​1016/​j.​molimm.​2007.​08.​013.PubMedCrossRef
32.
Zurück zum Zitat Wimberly, H., Brown, J. R., Schalper, K., Haack, H., Silver, M. R., Nixon, C., et al. (2015). PD-L1 expression correlates with tumor-infiltrating lymphocytes and response to neoadjuvant chemotherapy in breast cancer. Cancer Immunology Research, 3(4), 326–332. doi:10.1158/2326-6066.CIR-14-0133.PubMedCrossRef Wimberly, H., Brown, J. R., Schalper, K., Haack, H., Silver, M. R., Nixon, C., et al. (2015). PD-L1 expression correlates with tumor-infiltrating lymphocytes and response to neoadjuvant chemotherapy in breast cancer. Cancer Immunology Research, 3(4), 326–332. doi:10.​1158/​2326-6066.​CIR-14-0133.PubMedCrossRef
33.
Zurück zum Zitat Verbrugge, I., Hagekyriakou, J., Sharp, L. L., Galli, M., West, A., McLaughlin, N. M., et al. (2012). Radiotherapy increases the permissiveness of established mammary tumors to rejection by immunomodulatory antibodies. Cancer Research, 72(13), 3163–3174. doi:10.1158/0008-5472.CAN-12-0210.PubMedCrossRef Verbrugge, I., Hagekyriakou, J., Sharp, L. L., Galli, M., West, A., McLaughlin, N. M., et al. (2012). Radiotherapy increases the permissiveness of established mammary tumors to rejection by immunomodulatory antibodies. Cancer Research, 72(13), 3163–3174. doi:10.​1158/​0008-5472.​CAN-12-0210.PubMedCrossRef
35.
Zurück zum Zitat Stagg, J., Loi, S., Divisekera, U., Ngiow, S. F., Duret, H., Yagita, H., et al. (2011). Anti-ErbB-2 mAb therapy requires type I and II interferons and synergizes with anti-PD-1 or anti-CD137 mAb therapy. Proceedings of the National Academy of Sciences of the United States of America, 108(17), 7142–7147. doi:10.1073/pnas.1016569108.PubMedPubMedCentralCrossRef Stagg, J., Loi, S., Divisekera, U., Ngiow, S. F., Duret, H., Yagita, H., et al. (2011). Anti-ErbB-2 mAb therapy requires type I and II interferons and synergizes with anti-PD-1 or anti-CD137 mAb therapy. Proceedings of the National Academy of Sciences of the United States of America, 108(17), 7142–7147. doi:10.​1073/​pnas.​1016569108.PubMedPubMedCentralCrossRef
38.
Zurück zum Zitat Weber, J. S., D'Angelo, S. P., Minor, D., Hodi, F. S., Gutzmer, R., Neyns, B., et al. (2015). Nivolumab versus chemotherapy in patients with advanced melanoma who progressed after anti-CTLA-4 treatment (CheckMate 037): a randomised, controlled, open-label, phase 3 trial. The Lancet Oncology, 16(4), 375–384. doi:10.1016/S1470-2045(15)70076-8.PubMedCrossRef Weber, J. S., D'Angelo, S. P., Minor, D., Hodi, F. S., Gutzmer, R., Neyns, B., et al. (2015). Nivolumab versus chemotherapy in patients with advanced melanoma who progressed after anti-CTLA-4 treatment (CheckMate 037): a randomised, controlled, open-label, phase 3 trial. The Lancet Oncology, 16(4), 375–384. doi:10.​1016/​S1470-2045(15)70076-8.PubMedCrossRef
39.
Zurück zum Zitat Brahmer, J., Reckamp, K. L., Baas, P., Crino, L., Eberhardt, W. E., Poddubskaya, E., et al. (2015). Nivolumab versus docetaxel in advanced squamous-cell non-small-cell lung cancer. The New England Journal of Medicine, 373(2), 123–135. doi:10.1056/NEJMoa1504627.PubMedPubMedCentralCrossRef Brahmer, J., Reckamp, K. L., Baas, P., Crino, L., Eberhardt, W. E., Poddubskaya, E., et al. (2015). Nivolumab versus docetaxel in advanced squamous-cell non-small-cell lung cancer. The New England Journal of Medicine, 373(2), 123–135. doi:10.​1056/​NEJMoa1504627.PubMedPubMedCentralCrossRef
40.
Zurück zum Zitat Motzer, R. J., Escudier, B., McDermott, D. F., George, S., Hammers, H. J., Srinivas, S., et al. (2015). Nivolumab versus everolimus in advanced renal-cell carcinoma. The New England Journal of Medicine, 373(19), 1803–1813. doi:10.1056/NEJMoa1510665.PubMedCrossRef Motzer, R. J., Escudier, B., McDermott, D. F., George, S., Hammers, H. J., Srinivas, S., et al. (2015). Nivolumab versus everolimus in advanced renal-cell carcinoma. The New England Journal of Medicine, 373(19), 1803–1813. doi:10.​1056/​NEJMoa1510665.PubMedCrossRef
41.
Zurück zum Zitat Robert, C., Ribas, A., Wolchok, J. D., Hodi, F. S., Hamid, O., Kefford, R., et al. (2014). Anti-programmed-death-receptor-1 treatment with pembrolizumab in ipilimumab-refractory advanced melanoma: a randomised dose-comparison cohort of a phase 1 trial. Lancet, 384(9948), 1109–1117. doi:10.1016/S0140-6736(14)60958-2.PubMedCrossRef Robert, C., Ribas, A., Wolchok, J. D., Hodi, F. S., Hamid, O., Kefford, R., et al. (2014). Anti-programmed-death-receptor-1 treatment with pembrolizumab in ipilimumab-refractory advanced melanoma: a randomised dose-comparison cohort of a phase 1 trial. Lancet, 384(9948), 1109–1117. doi:10.​1016/​S0140-6736(14)60958-2.PubMedCrossRef
42.
Zurück zum Zitat Garon, E. B., Rizvi, N. A., Hui, R., Leighl, N., Balmanoukian, A. S., Eder, J. P., et al. (2015). Pembrolizumab for the treatment of non-small-cell lung cancer. The New England Journal of Medicine, 372(21), 2018–2028. doi:10.1056/NEJMoa1501824.PubMedCrossRef Garon, E. B., Rizvi, N. A., Hui, R., Leighl, N., Balmanoukian, A. S., Eder, J. P., et al. (2015). Pembrolizumab for the treatment of non-small-cell lung cancer. The New England Journal of Medicine, 372(21), 2018–2028. doi:10.​1056/​NEJMoa1501824.PubMedCrossRef
43.
Zurück zum Zitat Nanda, R., Chow, L. Q., Dees, E. C., Berger, R., Gupta, S., Geva, R., et al. (2015). Abstract S1-09: A phase Ib study of pembrolizumab (MK-3475) in patients with advanced triple-negative breast cancer. Cancer Res, 75(9 Supplement), S1-09-S01-09. Nanda, R., Chow, L. Q., Dees, E. C., Berger, R., Gupta, S., Geva, R., et al. (2015). Abstract S1-09: A phase Ib study of pembrolizumab (MK-3475) in patients with advanced triple-negative breast cancer. Cancer Res, 75(9 Supplement), S1-09-S01-09.
44.
Zurück zum Zitat Rugo, H., Delord, J., Im, S., Ott, P., Piha-Paul, S., Bedard, P., et al. (2016). Abstract S5-07: Preliminary efficacy and safety of pembrolizumab (MK-3475) in patients with PD-L1–positive, estrogen receptor-positive (ER+)/HER2-negative advanced breast cancer enrolled in KEYNOTE-028. Cancer Res, 76(4 Supplement), S5-07-S05-07. Rugo, H., Delord, J., Im, S., Ott, P., Piha-Paul, S., Bedard, P., et al. (2016). Abstract S5-07: Preliminary efficacy and safety of pembrolizumab (MK-3475) in patients with PD-L1–positive, estrogen receptor-positive (ER+)/HER2-negative advanced breast cancer enrolled in KEYNOTE-028. Cancer Res, 76(4 Supplement), S5-07-S05-07.
45.
Zurück zum Zitat Cimino-Mathews, A., Foote, J. B., & Emens, L. A. (2015). Immune targeting in breast cancer. Oncology (Williston Park), 29(5), 375–385. Cimino-Mathews, A., Foote, J. B., & Emens, L. A. (2015). Immune targeting in breast cancer. Oncology (Williston Park), 29(5), 375–385.
46.
Zurück zum Zitat Emens, L. A., Braiteh, F. S., Cassier, P., DeLord, J.-P., Eder, J. P., Shen, X., et al. (2015). Abstract PD1-6: Inhibition of PD-L1 by MPDL3280A leads to clinical activity in patients with metastatic triple-negative breast cancer. Cancer Res, 75(9 Supplement), PD1-6-PD1-6. Emens, L. A., Braiteh, F. S., Cassier, P., DeLord, J.-P., Eder, J. P., Shen, X., et al. (2015). Abstract PD1-6: Inhibition of PD-L1 by MPDL3280A leads to clinical activity in patients with metastatic triple-negative breast cancer. Cancer Res, 75(9 Supplement), PD1-6-PD1-6.
47.
Zurück zum Zitat Adams S, D. J., Hamilton E, et al. (December 8–12, 2015). Safety and clinical activity of atezolizumab (anti-PDL1) in combination with nab-paclitaxel in patients with metastatic triple-negative breast cancer. Presented at: San Antonio Breast Cancer Symposium; San Antonio, TX. Adams S, D. J., Hamilton E, et al. (December 8–12, 2015). Safety and clinical activity of atezolizumab (anti-PDL1) in combination with nab-paclitaxel in patients with metastatic triple-negative breast cancer. Presented at: San Antonio Breast Cancer Symposium; San Antonio, TX.
48.
Zurück zum Zitat Dirix, L., Takacs, I., Nikolinakos, P., Jerusalem, G., Arkenau, H., Hamilton, E., et al. (2016). Abstract S1-04: Avelumab (MSB0010718C), an anti-PD-L1 antibody, in patients with locally advanced or metastatic breast cancer: A phase Ib JAVELIN solid tumor trial. Cancer Res, 76(4 Supplement), S1-04-S01-04. Dirix, L., Takacs, I., Nikolinakos, P., Jerusalem, G., Arkenau, H., Hamilton, E., et al. (2016). Abstract S1-04: Avelumab (MSB0010718C), an anti-PD-L1 antibody, in patients with locally advanced or metastatic breast cancer: A phase Ib JAVELIN solid tumor trial. Cancer Res, 76(4 Supplement), S1-04-S01-04.
50.
Zurück zum Zitat Denkert, C., Loibl, S., Noske, A., Roller, M., Muller, B. M., Komor, M., et al. (2010). Tumor-associated lymphocytes as an independent predictor of response to neoadjuvant chemotherapy in breast cancer. Journal of Clinical Oncology, 28(1), 105–113. doi:10.1200/JCO.2009.23.7370.PubMedCrossRef Denkert, C., Loibl, S., Noske, A., Roller, M., Muller, B. M., Komor, M., et al. (2010). Tumor-associated lymphocytes as an independent predictor of response to neoadjuvant chemotherapy in breast cancer. Journal of Clinical Oncology, 28(1), 105–113. doi:10.​1200/​JCO.​2009.​23.​7370.PubMedCrossRef
51.
Zurück zum Zitat West, N. R., Milne, K., Truong, P. T., Macpherson, N., Nelson, B. H., & Watson, P. H. (2011). Tumor-infiltrating lymphocytes predict response to anthracycline-based chemotherapy in estrogen receptor-negative breast cancer. Breast Cancer Research, 13(6), R126. doi:10.1186/bcr3072.PubMedPubMedCentralCrossRef West, N. R., Milne, K., Truong, P. T., Macpherson, N., Nelson, B. H., & Watson, P. H. (2011). Tumor-infiltrating lymphocytes predict response to anthracycline-based chemotherapy in estrogen receptor-negative breast cancer. Breast Cancer Research, 13(6), R126. doi:10.​1186/​bcr3072.PubMedPubMedCentralCrossRef
52.
Zurück zum Zitat Ladoire, S., Mignot, G., Dabakuyo, S., Arnould, L., Apetoh, L., Rebe, C., et al. (2011). In situ immune response after neoadjuvant chemotherapy for breast cancer predicts survival. The Journal of Pathology, 224(3), 389–400. doi:10.1002/path.2866.PubMedCrossRef Ladoire, S., Mignot, G., Dabakuyo, S., Arnould, L., Apetoh, L., Rebe, C., et al. (2011). In situ immune response after neoadjuvant chemotherapy for breast cancer predicts survival. The Journal of Pathology, 224(3), 389–400. doi:10.​1002/​path.​2866.PubMedCrossRef
55.
Zurück zum Zitat Bates, G. J., Fox, S. B., Han, C., Leek, R. D., Garcia, J. F., Harris, A. L., et al. (2006). Quantification of regulatory T cells enables the identification of high-risk breast cancer patients and those at risk of late relapse. Journal of Clinical Oncology, 24(34), 5373–5380. doi:10.1200/JCO.2006.05.9584.PubMedCrossRef Bates, G. J., Fox, S. B., Han, C., Leek, R. D., Garcia, J. F., Harris, A. L., et al. (2006). Quantification of regulatory T cells enables the identification of high-risk breast cancer patients and those at risk of late relapse. Journal of Clinical Oncology, 24(34), 5373–5380. doi:10.​1200/​JCO.​2006.​05.​9584.PubMedCrossRef
56.
57.
Zurück zum Zitat Gobert, M., Treilleux, I., Bendriss-Vermare, N., Bachelot, T., Goddard-Leon, S., Arfi, V., et al. (2009). Regulatory T cells recruited through CCL22/CCR4 are selectively activated in lymphoid infiltrates surrounding primary breast tumors and lead to an adverse clinical outcome. Cancer Research, 69(5), 2000–2009. doi:10.1158/0008-5472.CAN-08-2360.PubMedCrossRef Gobert, M., Treilleux, I., Bendriss-Vermare, N., Bachelot, T., Goddard-Leon, S., Arfi, V., et al. (2009). Regulatory T cells recruited through CCL22/CCR4 are selectively activated in lymphoid infiltrates surrounding primary breast tumors and lead to an adverse clinical outcome. Cancer Research, 69(5), 2000–2009. doi:10.​1158/​0008-5472.​CAN-08-2360.PubMedCrossRef
59.
Zurück zum Zitat Joffroy, C. M., Buck, M. B., Stope, M. B., Popp, S. L., Pfizenmaier, K., & Knabbe, C. (2010). Antiestrogens induce transforming growth factor beta-mediated immunosuppression in breast cancer. Cancer Research, 70(4), 1314–1322. doi:10.1158/0008-5472.CAN-09-3292.PubMedCrossRef Joffroy, C. M., Buck, M. B., Stope, M. B., Popp, S. L., Pfizenmaier, K., & Knabbe, C. (2010). Antiestrogens induce transforming growth factor beta-mediated immunosuppression in breast cancer. Cancer Research, 70(4), 1314–1322. doi:10.​1158/​0008-5472.​CAN-09-3292.PubMedCrossRef
60.
Zurück zum Zitat Rech, A. J., Mick, R., Martin, S., Recio, A., Aqui, N. A., Powell Jr., D. J., et al. (2012). CD25 blockade depletes and selectively reprograms regulatory T cells in concert with immunotherapy in cancer patients. Science Translational Medicine, 4(134), 134ra162. doi:10.1126/scitranslmed.3003330.CrossRef Rech, A. J., Mick, R., Martin, S., Recio, A., Aqui, N. A., Powell Jr., D. J., et al. (2012). CD25 blockade depletes and selectively reprograms regulatory T cells in concert with immunotherapy in cancer patients. Science Translational Medicine, 4(134), 134ra162. doi:10.​1126/​scitranslmed.​3003330.CrossRef
65.
Zurück zum Zitat Diaz-Montero, C. M., Salem, M. L., Nishimura, M. I., Garrett-Mayer, E., Cole, D. J., & Montero, A. J. (2009). Increased circulating myeloid-derived suppressor cells correlate with clinical cancer stage, metastatic tumor burden, and doxorubicin-cyclophosphamide chemotherapy. Cancer Immunology, Immunotherapy, 58(1), 49–59. doi:10.1007/s00262-008-0523-4.PubMedCrossRef Diaz-Montero, C. M., Salem, M. L., Nishimura, M. I., Garrett-Mayer, E., Cole, D. J., & Montero, A. J. (2009). Increased circulating myeloid-derived suppressor cells correlate with clinical cancer stage, metastatic tumor burden, and doxorubicin-cyclophosphamide chemotherapy. Cancer Immunology, Immunotherapy, 58(1), 49–59. doi:10.​1007/​s00262-008-0523-4.PubMedCrossRef
66.
Zurück zum Zitat Sinha, P., Clements, V. K., & Ostrand-Rosenberg, S. (2005). Reduction of myeloid-derived suppressor cells and induction of M1 macrophages facilitate the rejection of established metastatic disease. Journal of Immunology, 174(2), 636–645.CrossRef Sinha, P., Clements, V. K., & Ostrand-Rosenberg, S. (2005). Reduction of myeloid-derived suppressor cells and induction of M1 macrophages facilitate the rejection of established metastatic disease. Journal of Immunology, 174(2), 636–645.CrossRef
67.
Zurück zum Zitat Morales, J. K., Kmieciak, M., Graham, L., Feldmesser, M., Bear, H. D., & Manjili, M. H. (2009). Adoptive transfer of HER2/neu-specific T cells expanded with alternating gamma chain cytokines mediate tumor regression when combined with the depletion of myeloid-derived suppressor cells. Cancer Immunology, Immunotherapy, 58(6), 941–953. doi:10.1007/s00262-008-0609-z.PubMedCrossRef Morales, J. K., Kmieciak, M., Graham, L., Feldmesser, M., Bear, H. D., & Manjili, M. H. (2009). Adoptive transfer of HER2/neu-specific T cells expanded with alternating gamma chain cytokines mediate tumor regression when combined with the depletion of myeloid-derived suppressor cells. Cancer Immunology, Immunotherapy, 58(6), 941–953. doi:10.​1007/​s00262-008-0609-z.PubMedCrossRef
69.
Zurück zum Zitat Thakur, A., Schalk, D., Sarkar, S. H., Al-Khadimi, Z., Sarkar, F. H., & Lum, L. G. (2012). A Th1 cytokine-enriched microenvironment enhances tumor killing by activated T cells armed with bispecific antibodies and inhibits the development of myeloid-derived suppressor cells. Cancer Immunology, Immunotherapy, 61(4), 497–509. doi:10.1007/s00262-011-1116-1.PubMedCrossRef Thakur, A., Schalk, D., Sarkar, S. H., Al-Khadimi, Z., Sarkar, F. H., & Lum, L. G. (2012). A Th1 cytokine-enriched microenvironment enhances tumor killing by activated T cells armed with bispecific antibodies and inhibits the development of myeloid-derived suppressor cells. Cancer Immunology, Immunotherapy, 61(4), 497–509. doi:10.​1007/​s00262-011-1116-1.PubMedCrossRef
70.
Zurück zum Zitat Montero, A. J., Diaz-Montero, C. M., Deutsch, Y. E., Hurley, J., Koniaris, L. G., Rumboldt, T., et al. (2012). Phase 2 study of neoadjuvant treatment with NOV-002 in combination with doxorubicin and cyclophosphamide followed by docetaxel in patients with HER-2 negative clinical stage II-IIIc breast cancer. Breast Cancer Research and Treatment, 132(1), 215–223. doi:10.1007/s10549-011-1889-0.PubMedCrossRef Montero, A. J., Diaz-Montero, C. M., Deutsch, Y. E., Hurley, J., Koniaris, L. G., Rumboldt, T., et al. (2012). Phase 2 study of neoadjuvant treatment with NOV-002 in combination with doxorubicin and cyclophosphamide followed by docetaxel in patients with HER-2 negative clinical stage II-IIIc breast cancer. Breast Cancer Research and Treatment, 132(1), 215–223. doi:10.​1007/​s10549-011-1889-0.PubMedCrossRef
71.
73.
Zurück zum Zitat Isla Larrain, M. T., Rabassa, M. E., Lacunza, E., Barbera, A., Creton, A., Segal-Eiras, A., et al. (2014). IDO is highly expressed in breast cancer and breast cancer-derived circulating microvesicles and associated to aggressive types of tumors by in silico analysis. Tumour Biology, 35(7), 6511–6519. doi:10.1007/s13277-014-1859-3.PubMedCrossRef Isla Larrain, M. T., Rabassa, M. E., Lacunza, E., Barbera, A., Creton, A., Segal-Eiras, A., et al. (2014). IDO is highly expressed in breast cancer and breast cancer-derived circulating microvesicles and associated to aggressive types of tumors by in silico analysis. Tumour Biology, 35(7), 6511–6519. doi:10.​1007/​s13277-014-1859-3.PubMedCrossRef
74.
Zurück zum Zitat Li, R., Wei, F., Yu, J., Li, H., Ren, X., & Hao, X. (2009). IDO inhibits T-cell function through suppressing Vav1 expression and activation. Cancer Biology & Therapy, 8(14), 1402–1408.CrossRef Li, R., Wei, F., Yu, J., Li, H., Ren, X., & Hao, X. (2009). IDO inhibits T-cell function through suppressing Vav1 expression and activation. Cancer Biology & Therapy, 8(14), 1402–1408.CrossRef
75.
Zurück zum Zitat Sun, J., Yu, J., Li, H., Yang, L., Wei, F., Yu, W., et al. (2011). Upregulated expression of indoleamine 2, 3-dioxygenase in CHO cells induces apoptosis of competent T cells and increases proportion of Treg cells. Journal of Experimental & Clinical Cancer Research, 30, 82. doi:10.1186/1756-9966-30-82.CrossRef Sun, J., Yu, J., Li, H., Yang, L., Wei, F., Yu, W., et al. (2011). Upregulated expression of indoleamine 2, 3-dioxygenase in CHO cells induces apoptosis of competent T cells and increases proportion of Treg cells. Journal of Experimental & Clinical Cancer Research, 30, 82. doi:10.​1186/​1756-9966-30-82.CrossRef
77.
Zurück zum Zitat Yu, J., Du, W., Yan, F., Wang, Y., Li, H., Cao, S., et al. (2013). Myeloid-derived suppressor cells suppress antitumor immune responses through IDO expression and correlate with lymph node metastasis in patients with breast cancer. Journal of Immunology, 190(7), 3783–3797. doi:10.4049/jimmunol.1201449.CrossRef Yu, J., Du, W., Yan, F., Wang, Y., Li, H., Cao, S., et al. (2013). Myeloid-derived suppressor cells suppress antitumor immune responses through IDO expression and correlate with lymph node metastasis in patients with breast cancer. Journal of Immunology, 190(7), 3783–3797. doi:10.​4049/​jimmunol.​1201449.CrossRef
78.
Zurück zum Zitat Muller, A. J., DuHadaway, J. B., Donover, P. S., Sutanto-Ward, E., & Prendergast, G. C. (2005). Inhibition of indoleamine 2,3-dioxygenase, an immunoregulatory target of the cancer suppression gene Bin1, potentiates cancer chemotherapy. Nature Medicine, 11(3), 312–319. doi:10.1038/nm1196.PubMedCrossRef Muller, A. J., DuHadaway, J. B., Donover, P. S., Sutanto-Ward, E., & Prendergast, G. C. (2005). Inhibition of indoleamine 2,3-dioxygenase, an immunoregulatory target of the cancer suppression gene Bin1, potentiates cancer chemotherapy. Nature Medicine, 11(3), 312–319. doi:10.​1038/​nm1196.PubMedCrossRef
79.
Zurück zum Zitat Soliman, H. H., Jackson, E., Neuger, T., Dees, E. C., Harvey, R. D., Han, H., et al. (2014). A first in man phase I trial of the oral immunomodulator, indoximod, combined with docetaxel in patients with metastatic solid tumors. Oncotarget, 5(18), 8136–8146.PubMedPubMedCentralCrossRef Soliman, H. H., Jackson, E., Neuger, T., Dees, E. C., Harvey, R. D., Han, H., et al. (2014). A first in man phase I trial of the oral immunomodulator, indoximod, combined with docetaxel in patients with metastatic solid tumors. Oncotarget, 5(18), 8136–8146.PubMedPubMedCentralCrossRef
80.
Zurück zum Zitat Tang, S., Montero, A., Munn, D., Link, C., Vahanian, N., Kennedy, E., et al. (2016). Abstract P2-11-09: A phase 2 randomized trial of the IDO pathway inhibitor indoximod in combination with taxane based chemotherapy for metastatic breast cancer: Preliminary data. Cancer Res, 76(4 Supplement), P2-11-09-P12-11-09. Tang, S., Montero, A., Munn, D., Link, C., Vahanian, N., Kennedy, E., et al. (2016). Abstract P2-11-09: A phase 2 randomized trial of the IDO pathway inhibitor indoximod in combination with taxane based chemotherapy for metastatic breast cancer: Preliminary data. Cancer Res, 76(4 Supplement), P2-11-09-P12-11-09.
82.
Zurück zum Zitat Laoui, D., Movahedi, K., Van Overmeire, E., Van den Bossche, J., Schouppe, E., Mommer, C., et al. (2011). Tumor-associated macrophages in breast cancer: distinct subsets, distinct functions. The International Journal of Developmental Biology, 55(7–9), 861–867. doi:10.1387/ijdb.113371dl.PubMedCrossRef Laoui, D., Movahedi, K., Van Overmeire, E., Van den Bossche, J., Schouppe, E., Mommer, C., et al. (2011). Tumor-associated macrophages in breast cancer: distinct subsets, distinct functions. The International Journal of Developmental Biology, 55(7–9), 861–867. doi:10.​1387/​ijdb.​113371dl.PubMedCrossRef
85.
Zurück zum Zitat Leek, R. D., Lewis, C. E., Whitehouse, R., Greenall, M., Clarke, J., & Harris, A. L. (1996). Association of macrophage infiltration with angiogenesis and prognosis in invasive breast carcinoma. Cancer Research, 56(20), 4625–4629.PubMed Leek, R. D., Lewis, C. E., Whitehouse, R., Greenall, M., Clarke, J., & Harris, A. L. (1996). Association of macrophage infiltration with angiogenesis and prognosis in invasive breast carcinoma. Cancer Research, 56(20), 4625–4629.PubMed
86.
Zurück zum Zitat Tsutsui, S., Yasuda, K., Suzuki, K., Tahara, K., Higashi, H., & Era, S. (2005). Macrophage infiltration and its prognostic implications in breast cancer: the relationship with VEGF expression and microvessel density. Oncology Reports, 14(2), 425–431.PubMed Tsutsui, S., Yasuda, K., Suzuki, K., Tahara, K., Higashi, H., & Era, S. (2005). Macrophage infiltration and its prognostic implications in breast cancer: the relationship with VEGF expression and microvessel density. Oncology Reports, 14(2), 425–431.PubMed
87.
Zurück zum Zitat Mahmoud, S. M., Lee, A. H., Paish, E. C., Macmillan, R. D., Ellis, I. O., & Green, A. R. (2012). Tumour-infiltrating macrophages and clinical outcome in breast cancer. Journal of Clinical Pathology, 65(2), 159–163. doi:10.1136/jclinpath-2011-200355.PubMedCrossRef Mahmoud, S. M., Lee, A. H., Paish, E. C., Macmillan, R. D., Ellis, I. O., & Green, A. R. (2012). Tumour-infiltrating macrophages and clinical outcome in breast cancer. Journal of Clinical Pathology, 65(2), 159–163. doi:10.​1136/​jclinpath-2011-200355.PubMedCrossRef
88.
Zurück zum Zitat Campbell, M. J., Tonlaar, N. Y., Garwood, E. R., Huo, D., Moore, D. H., Khramtsov, A. I., et al. (2011). Proliferating macrophages associated with high grade, hormone receptor negative breast cancer and poor clinical outcome. Breast Cancer Research and Treatment, 128(3), 703–711. doi:10.1007/s10549-010-1154-y.PubMedCrossRef Campbell, M. J., Tonlaar, N. Y., Garwood, E. R., Huo, D., Moore, D. H., Khramtsov, A. I., et al. (2011). Proliferating macrophages associated with high grade, hormone receptor negative breast cancer and poor clinical outcome. Breast Cancer Research and Treatment, 128(3), 703–711. doi:10.​1007/​s10549-010-1154-y.PubMedCrossRef
90.
92.
Zurück zum Zitat Huang, Y., Yuan, J., Righi, E., Kamoun, W. S., Ancukiewicz, M., Nezivar, J., et al. (2012). Vascular normalizing doses of antiangiogenic treatment reprogram the immunosuppressive tumor microenvironment and enhance immunotherapy. Proceedings of the National Academy of Sciences of the United States of America, 109(43), 17561–17566. doi:10.1073/pnas.1215397109.PubMedPubMedCentralCrossRef Huang, Y., Yuan, J., Righi, E., Kamoun, W. S., Ancukiewicz, M., Nezivar, J., et al. (2012). Vascular normalizing doses of antiangiogenic treatment reprogram the immunosuppressive tumor microenvironment and enhance immunotherapy. Proceedings of the National Academy of Sciences of the United States of America, 109(43), 17561–17566. doi:10.​1073/​pnas.​1215397109.PubMedPubMedCentralCrossRef
97.
Zurück zum Zitat Dirkx, A. E., Oude Egbrink, M. G., Wagstaff, J., & Griffioen, A. W. (2006). Monocyte/macrophage infiltration in tumors: modulators of angiogenesis. Journal of Leukocyte Biology, 80(6), 1183–1196. doi:10.1189/jlb.0905495.PubMedCrossRef Dirkx, A. E., Oude Egbrink, M. G., Wagstaff, J., & Griffioen, A. W. (2006). Monocyte/macrophage infiltration in tumors: modulators of angiogenesis. Journal of Leukocyte Biology, 80(6), 1183–1196. doi:10.​1189/​jlb.​0905495.PubMedCrossRef
100.
Zurück zum Zitat Yang, J., Liao, D., Chen, C., Liu, Y., Chuang, T. H., Xiang, R., et al. (2013). Tumor-associated macrophages regulate murine breast cancer stem cells through a novel paracrine EGFR/Stat3/Sox-2 signaling pathway. Stem Cells, 31(2), 248–258. doi:10.1002/stem.1281.PubMedCrossRef Yang, J., Liao, D., Chen, C., Liu, Y., Chuang, T. H., Xiang, R., et al. (2013). Tumor-associated macrophages regulate murine breast cancer stem cells through a novel paracrine EGFR/Stat3/Sox-2 signaling pathway. Stem Cells, 31(2), 248–258. doi:10.​1002/​stem.​1281.PubMedCrossRef
103.
Zurück zum Zitat Salgado, R., Junius, S., Benoy, I., Van Dam, P., Vermeulen, P., Van Marck, E., et al. (2003). Circulating interleukin-6 predicts survival in patients with metastatic breast cancer. International Journal of Cancer, 103(5), 642–646. doi:10.1002/ijc.10833.PubMedCrossRef Salgado, R., Junius, S., Benoy, I., Van Dam, P., Vermeulen, P., Van Marck, E., et al. (2003). Circulating interleukin-6 predicts survival in patients with metastatic breast cancer. International Journal of Cancer, 103(5), 642–646. doi:10.​1002/​ijc.​10833.PubMedCrossRef
106.
Zurück zum Zitat Marotta, L. L., Almendro, V., Marusyk, A., Shipitsin, M., Schemme, J., Walker, S. R., et al. (2011). The JAK2/STAT3 signaling pathway is required for growth of CD44(+)CD24(−) stem cell-like breast cancer cells in human tumors. The Journal of Clinical Investigation, 121(7), 2723–2735. doi:10.1172/JCI44745.PubMedPubMedCentralCrossRef Marotta, L. L., Almendro, V., Marusyk, A., Shipitsin, M., Schemme, J., Walker, S. R., et al. (2011). The JAK2/STAT3 signaling pathway is required for growth of CD44(+)CD24(−) stem cell-like breast cancer cells in human tumors. The Journal of Clinical Investigation, 121(7), 2723–2735. doi:10.​1172/​JCI44745.PubMedPubMedCentralCrossRef
107.
108.
Zurück zum Zitat Hartman, Z. C., Poage, G. M., den Hollander, P., Tsimelzon, A., Hill, J., Panupinthu, N., et al. (2013). Growth of triple-negative breast cancer cells relies upon coordinate autocrine expression of the proinflammatory cytokines IL-6 and IL-8. Cancer Research, 73(11), 3470–3480. doi:10.1158/0008-5472.CAN-12-4524-T.PubMedCrossRef Hartman, Z. C., Poage, G. M., den Hollander, P., Tsimelzon, A., Hill, J., Panupinthu, N., et al. (2013). Growth of triple-negative breast cancer cells relies upon coordinate autocrine expression of the proinflammatory cytokines IL-6 and IL-8. Cancer Research, 73(11), 3470–3480. doi:10.​1158/​0008-5472.​CAN-12-4524-T.PubMedCrossRef
109.
Zurück zum Zitat Xie, G., Yao, Q., Liu, Y., Du, S., Liu, A., Guo, Z., et al. (2012). IL-6-induced epithelial-mesenchymal transition promotes the generation of breast cancer stem-like cells analogous to mammosphere cultures. International Journal of Oncology, 40(4), 1171–1179. doi:10.3892/ijo.2011.1275.PubMed Xie, G., Yao, Q., Liu, Y., Du, S., Liu, A., Guo, Z., et al. (2012). IL-6-induced epithelial-mesenchymal transition promotes the generation of breast cancer stem-like cells analogous to mammosphere cultures. International Journal of Oncology, 40(4), 1171–1179. doi:10.​3892/​ijo.​2011.​1275.PubMed
110.
Zurück zum Zitat Hwang, M. S., Yu, N., Stinson, S. Y., Yue, P., Newman, R. J., Allan, B. B., et al. (2013). miR-221/222 targets adiponectin receptor 1 to promote the epithelial-to-mesenchymal transition in breast cancer. PLoS One, 8(6), e66502, doi:10.1371/journal.pone.0066502. Hwang, M. S., Yu, N., Stinson, S. Y., Yue, P., Newman, R. J., Allan, B. B., et al. (2013). miR-221/222 targets adiponectin receptor 1 to promote the epithelial-to-mesenchymal transition in breast cancer. PLoS One, 8(6), e66502, doi:10.1371/journal.pone.0066502.
111.
Zurück zum Zitat Britschgi, A., Andraos, R., Brinkhaus, H., Klebba, I., Romanet, V., Muller, U., et al. (2012). JAK2/STAT5 inhibition circumvents resistance to PI3K/mTOR blockade: a rationale for cotargeting these pathways in metastatic breast cancer. Cancer Cell, 22(6), 796–811. doi:10.1016/j.ccr.2012.10.023.PubMedCrossRef Britschgi, A., Andraos, R., Brinkhaus, H., Klebba, I., Romanet, V., Muller, U., et al. (2012). JAK2/STAT5 inhibition circumvents resistance to PI3K/mTOR blockade: a rationale for cotargeting these pathways in metastatic breast cancer. Cancer Cell, 22(6), 796–811. doi:10.​1016/​j.​ccr.​2012.​10.​023.PubMedCrossRef
113.
Zurück zum Zitat Buzdar, A. U., Ibrahim, N. K., Francis, D., Booser, D. J., Thomas, E. S., Theriault, R. L., et al. (2005). Significantly higher pathologic complete remission rate after neoadjuvant therapy with trastuzumab, paclitaxel, and epirubicin chemotherapy: results of a randomized trial in human epidermal growth factor receptor 2-positive operable breast cancer. Journal of Clinical Oncology, 23(16), 3676–3685. doi:10.1200/JCO.2005.07.032.PubMedCrossRef Buzdar, A. U., Ibrahim, N. K., Francis, D., Booser, D. J., Thomas, E. S., Theriault, R. L., et al. (2005). Significantly higher pathologic complete remission rate after neoadjuvant therapy with trastuzumab, paclitaxel, and epirubicin chemotherapy: results of a randomized trial in human epidermal growth factor receptor 2-positive operable breast cancer. Journal of Clinical Oncology, 23(16), 3676–3685. doi:10.​1200/​JCO.​2005.​07.​032.PubMedCrossRef
114.
Zurück zum Zitat Gianni, L., Eiermann, W., Semiglazov, V., Manikhas, A., Lluch, A., Tjulandin, S., et al. (2010). Neoadjuvant chemotherapy with trastuzumab followed by adjuvant trastuzumab versus neoadjuvant chemotherapy alone, in patients with HER2-positive locally advanced breast cancer (the NOAH trial): a randomised controlled superiority trial with a parallel HER2-negative cohort. Lancet, 375(9712), 377–384. doi:10.1016/S0140-6736(09)61964-4.PubMedCrossRef Gianni, L., Eiermann, W., Semiglazov, V., Manikhas, A., Lluch, A., Tjulandin, S., et al. (2010). Neoadjuvant chemotherapy with trastuzumab followed by adjuvant trastuzumab versus neoadjuvant chemotherapy alone, in patients with HER2-positive locally advanced breast cancer (the NOAH trial): a randomised controlled superiority trial with a parallel HER2-negative cohort. Lancet, 375(9712), 377–384. doi:10.​1016/​S0140-6736(09)61964-4.PubMedCrossRef
116.
Zurück zum Zitat Gianni, L., Dafni, U., Gelber, R. D., Azambuja, E., Muehlbauer, S., Goldhirsch, A., et al. (2011). Treatment with trastuzumab for 1 year after adjuvant chemotherapy in patients with HER2-positive early breast cancer: a 4-year follow-up of a randomised controlled trial. The Lancet Oncology, 12(3), 236–244. doi:10.1016/S1470-2045(11)70033-X.PubMedCrossRef Gianni, L., Dafni, U., Gelber, R. D., Azambuja, E., Muehlbauer, S., Goldhirsch, A., et al. (2011). Treatment with trastuzumab for 1 year after adjuvant chemotherapy in patients with HER2-positive early breast cancer: a 4-year follow-up of a randomised controlled trial. The Lancet Oncology, 12(3), 236–244. doi:10.​1016/​S1470-2045(11)70033-X.PubMedCrossRef
118.
Zurück zum Zitat Huang, Y., Fu, P., & Fan, W. (2013). Novel targeted therapies to overcome trastuzumab resistance in HER2-overexpressing metastatic breast cancer. Current Drug Targets, 14(8), 889–898.PubMedCrossRef Huang, Y., Fu, P., & Fan, W. (2013). Novel targeted therapies to overcome trastuzumab resistance in HER2-overexpressing metastatic breast cancer. Current Drug Targets, 14(8), 889–898.PubMedCrossRef
119.
Zurück zum Zitat Nahta, R., Hung, M. C., & Esteva, F. J. (2004). The HER-2-targeting antibodies trastuzumab and pertuzumab synergistically inhibit the survival of breast cancer cells. Cancer Research, 64(7), 2343–2346.PubMedCrossRef Nahta, R., Hung, M. C., & Esteva, F. J. (2004). The HER-2-targeting antibodies trastuzumab and pertuzumab synergistically inhibit the survival of breast cancer cells. Cancer Research, 64(7), 2343–2346.PubMedCrossRef
120.
Zurück zum Zitat Agus, D. B., Akita, R. W., Fox, W. D., Lewis, G. D., Higgins, B., Pisacane, P. I., et al. (2002). Targeting ligand-activated ErbB2 signaling inhibits breast and prostate tumor growth. Cancer Cell, 2(2), 127–137.PubMedCrossRef Agus, D. B., Akita, R. W., Fox, W. D., Lewis, G. D., Higgins, B., Pisacane, P. I., et al. (2002). Targeting ligand-activated ErbB2 signaling inhibits breast and prostate tumor growth. Cancer Cell, 2(2), 127–137.PubMedCrossRef
121.
Zurück zum Zitat Franklin, M. C., Carey, K. D., Vajdos, F. F., Leahy, D. J., de Vos, A. M., & Sliwkowski, M. X. (2004). Insights into ErbB signaling from the structure of the ErbB2-pertuzumab complex. Cancer Cell, 5(4), 317–328.PubMedCrossRef Franklin, M. C., Carey, K. D., Vajdos, F. F., Leahy, D. J., de Vos, A. M., & Sliwkowski, M. X. (2004). Insights into ErbB signaling from the structure of the ErbB2-pertuzumab complex. Cancer Cell, 5(4), 317–328.PubMedCrossRef
122.
Zurück zum Zitat Scheuer, W., Friess, T., Burtscher, H., Bossenmaier, B., Endl, J., & Hasmann, M. (2009). Strongly enhanced antitumor activity of trastuzumab and pertuzumab combination treatment on HER2-positive human xenograft tumor models. Cancer Research, 69(24), 9330–9336. doi:10.1158/0008-5472.CAN-08-4597.PubMedCrossRef Scheuer, W., Friess, T., Burtscher, H., Bossenmaier, B., Endl, J., & Hasmann, M. (2009). Strongly enhanced antitumor activity of trastuzumab and pertuzumab combination treatment on HER2-positive human xenograft tumor models. Cancer Research, 69(24), 9330–9336. doi:10.​1158/​0008-5472.​CAN-08-4597.PubMedCrossRef
123.
Zurück zum Zitat Capelan, M., Pugliano, L., De Azambuja, E., Bozovic, I., Saini, K. S., Sotiriou, C., et al. (2013). Pertuzumab: new hope for patients with HER2-positive breast cancer. Annals of Oncology, 24(2), 273–282. doi:10.1093/annonc/mds328.PubMedCrossRef Capelan, M., Pugliano, L., De Azambuja, E., Bozovic, I., Saini, K. S., Sotiriou, C., et al. (2013). Pertuzumab: new hope for patients with HER2-positive breast cancer. Annals of Oncology, 24(2), 273–282. doi:10.​1093/​annonc/​mds328.PubMedCrossRef
124.
Zurück zum Zitat Swain, S. M., Kim, S. B., Cortes, J., Ro, J., Semiglazov, V., Campone, M., et al. (2013). Pertuzumab, trastuzumab, and docetaxel for HER2-positive metastatic breast cancer (CLEOPATRA study): overall survival results from a randomised, double-blind, placebo-controlled, phase 3 study. The Lancet Oncology, 14(6), 461–471. doi:10.1016/S1470-2045(13)70130-X.PubMedPubMedCentralCrossRef Swain, S. M., Kim, S. B., Cortes, J., Ro, J., Semiglazov, V., Campone, M., et al. (2013). Pertuzumab, trastuzumab, and docetaxel for HER2-positive metastatic breast cancer (CLEOPATRA study): overall survival results from a randomised, double-blind, placebo-controlled, phase 3 study. The Lancet Oncology, 14(6), 461–471. doi:10.​1016/​S1470-2045(13)70130-X.PubMedPubMedCentralCrossRef
125.
Zurück zum Zitat Gianni, L., Pienkowski, T., Im, Y. H., Roman, L., Tseng, L. M., Liu, M. C., et al. (2012). Efficacy and safety of neoadjuvant pertuzumab and trastuzumab in women with locally advanced, inflammatory, or early HER2-positive breast cancer (NeoSphere): a randomised multicentre, open-label, phase 2 trial. The Lancet Oncology, 13(1), 25–32. doi:10.1016/S1470-2045(11)70336-9.PubMedCrossRef Gianni, L., Pienkowski, T., Im, Y. H., Roman, L., Tseng, L. M., Liu, M. C., et al. (2012). Efficacy and safety of neoadjuvant pertuzumab and trastuzumab in women with locally advanced, inflammatory, or early HER2-positive breast cancer (NeoSphere): a randomised multicentre, open-label, phase 2 trial. The Lancet Oncology, 13(1), 25–32. doi:10.​1016/​S1470-2045(11)70336-9.PubMedCrossRef
127.
Zurück zum Zitat Musolino, A., Naldi, N., Bortesi, B., Pezzuolo, D., Capelletti, M., Missale, G., et al. (2008). Immunoglobulin G fragment C receptor polymorphisms and clinical efficacy of trastuzumab-based therapy in patients with HER-2/neu-positive metastatic breast cancer. Journal of Clinical Oncology, 26(11), 1789–1796. doi:10.1200/JCO.2007.14.8957.PubMedCrossRef Musolino, A., Naldi, N., Bortesi, B., Pezzuolo, D., Capelletti, M., Missale, G., et al. (2008). Immunoglobulin G fragment C receptor polymorphisms and clinical efficacy of trastuzumab-based therapy in patients with HER-2/neu-positive metastatic breast cancer. Journal of Clinical Oncology, 26(11), 1789–1796. doi:10.​1200/​JCO.​2007.​14.​8957.PubMedCrossRef
128.
Zurück zum Zitat Mellor, J. D., Brown, M. P., Irving, H. R., Zalcberg, J. R., & Dobrovic, A. (2013). A critical review of the role of Fc gamma receptor polymorphisms in the response to monoclonal antibodies in cancer. Journal of Hematology & Oncology, 6, 1. doi:10.1186/1756-8722-6-1.CrossRef Mellor, J. D., Brown, M. P., Irving, H. R., Zalcberg, J. R., & Dobrovic, A. (2013). A critical review of the role of Fc gamma receptor polymorphisms in the response to monoclonal antibodies in cancer. Journal of Hematology & Oncology, 6, 1. doi:10.​1186/​1756-8722-6-1.CrossRef
129.
132.
Zurück zum Zitat Vaughan, A. T., Iriyama, C., Beers, S. A., Chan, C. H., Lim, S. H., Williams, E. L., et al. (2014). Inhibitory FcgammaRIIb (CD32b) becomes activated by therapeutic mAb in both cis and trans and drives internalization according to antibody specificity. Blood, 123(5), 669–677. doi:10.1182/blood-2013-04-490821.PubMedCrossRef Vaughan, A. T., Iriyama, C., Beers, S. A., Chan, C. H., Lim, S. H., Williams, E. L., et al. (2014). Inhibitory FcgammaRIIb (CD32b) becomes activated by therapeutic mAb in both cis and trans and drives internalization according to antibody specificity. Blood, 123(5), 669–677. doi:10.​1182/​blood-2013-04-490821.PubMedCrossRef
133.
Zurück zum Zitat Schaefer, G., Haber, L., Crocker, L. M., Shia, S., Shao, L., Dowbenko, D., et al. (2011). A two-in-one antibody against HER3 and EGFR has superior inhibitory activity compared with monospecific antibodies. Cancer Cell, 20(4), 472–486. doi:10.1016/j.ccr.2011.09.003.PubMedCrossRef Schaefer, G., Haber, L., Crocker, L. M., Shia, S., Shao, L., Dowbenko, D., et al. (2011). A two-in-one antibody against HER3 and EGFR has superior inhibitory activity compared with monospecific antibodies. Cancer Cell, 20(4), 472–486. doi:10.​1016/​j.​ccr.​2011.​09.​003.PubMedCrossRef
134.
Zurück zum Zitat Bostrom, J., Yu, S. F., Kan, D., Appleton, B. A., Lee, C. V., Billeci, K., et al. (2009). Variants of the antibody herceptin that interact with HER2 and VEGF at the antigen binding site. Science, 323(5921), 1610–1614. doi:10.1126/science.1165480.PubMedCrossRef Bostrom, J., Yu, S. F., Kan, D., Appleton, B. A., Lee, C. V., Billeci, K., et al. (2009). Variants of the antibody herceptin that interact with HER2 and VEGF at the antigen binding site. Science, 323(5921), 1610–1614. doi:10.​1126/​science.​1165480.PubMedCrossRef
135.
Zurück zum Zitat Robinson, M. K., Hodge, K. M., Horak, E., Sundberg, A. L., Russeva, M., Shaller, C. C., et al. (2008). Targeting ErbB2 and ErbB3 with a bispecific single-chain Fv enhances targeting selectivity and induces a therapeutic effect in vitro. British Journal of Cancer, 99(9), 1415–1425. doi:10.1038/sj.bjc.6604700.PubMedPubMedCentralCrossRef Robinson, M. K., Hodge, K. M., Horak, E., Sundberg, A. L., Russeva, M., Shaller, C. C., et al. (2008). Targeting ErbB2 and ErbB3 with a bispecific single-chain Fv enhances targeting selectivity and induces a therapeutic effect in vitro. British Journal of Cancer, 99(9), 1415–1425. doi:10.​1038/​sj.​bjc.​6604700.PubMedPubMedCentralCrossRef
136.
Zurück zum Zitat McDonagh, C. F., Huhalov, A., Harms, B. D., Adams, S., Paragas, V., Oyama, S., et al. (2012). Antitumor activity of a novel bispecific antibody that targets the ErbB2/ErbB3 oncogenic unit and inhibits heregulin-induced activation of ErbB3. Molecular Cancer Therapeutics, 11(3), 582–593. doi:10.1158/1535-7163.MCT-11-0820.PubMedCrossRef McDonagh, C. F., Huhalov, A., Harms, B. D., Adams, S., Paragas, V., Oyama, S., et al. (2012). Antitumor activity of a novel bispecific antibody that targets the ErbB2/ErbB3 oncogenic unit and inhibits heregulin-induced activation of ErbB3. Molecular Cancer Therapeutics, 11(3), 582–593. doi:10.​1158/​1535-7163.​MCT-11-0820.PubMedCrossRef
137.
Zurück zum Zitat Oyama, S. K., Paragas, V., Adams, S., Luus, L., Huhalov, A., Kudla, A. J., et al. (2011). MM-111, an ErbB2/ErbB3 bispecific antibody, effectively combines with lapatinib to inhibit growth of ErbB2-overexpressing tumor cells. Cancer Research, 71(8 Supplement), 654.CrossRef Oyama, S. K., Paragas, V., Adams, S., Luus, L., Huhalov, A., Kudla, A. J., et al. (2011). MM-111, an ErbB2/ErbB3 bispecific antibody, effectively combines with lapatinib to inhibit growth of ErbB2-overexpressing tumor cells. Cancer Research, 71(8 Supplement), 654.CrossRef
139.
Zurück zum Zitat Heiss, M. M., Murawa, P., Koralewski, P., Kutarska, E., Kolesnik, O. O., Ivanchenko, V. V., et al. (2010). The trifunctional antibody catumaxomab for the treatment of malignant ascites due to epithelial cancer: results of a prospective randomized phase II/III trial. International Journal of Cancer, 127(9), 2209–2221. doi:10.1002/ijc.25423.PubMedPubMedCentralCrossRef Heiss, M. M., Murawa, P., Koralewski, P., Kutarska, E., Kolesnik, O. O., Ivanchenko, V. V., et al. (2010). The trifunctional antibody catumaxomab for the treatment of malignant ascites due to epithelial cancer: results of a prospective randomized phase II/III trial. International Journal of Cancer, 127(9), 2209–2221. doi:10.​1002/​ijc.​25423.PubMedPubMedCentralCrossRef
140.
Zurück zum Zitat Jager, M., Schoberth, A., Ruf, P., Hess, J., & Lindhofer, H. (2009). The trifunctional antibody ertumaxomab destroys tumor cells that express low levels of human epidermal growth factor receptor 2. Cancer Research, 69(10), 4270–4276. doi:10.1158/0008-5472.CAN-08-2861.PubMedCrossRef Jager, M., Schoberth, A., Ruf, P., Hess, J., & Lindhofer, H. (2009). The trifunctional antibody ertumaxomab destroys tumor cells that express low levels of human epidermal growth factor receptor 2. Cancer Research, 69(10), 4270–4276. doi:10.​1158/​0008-5472.​CAN-08-2861.PubMedCrossRef
141.
Zurück zum Zitat Topp, M. S., Gokbuget, N., Stein, A. S., Zugmaier, G., O'Brien, S., Bargou, R. C., et al. (2015). Safety and activity of blinatumomab for adult patients with relapsed or refractory B-precursor acute lymphoblastic leukaemia: a multicentre, single-arm, phase 2 study. The Lancet Oncology, 16(1), 57–66. doi:10.1016/S1470-2045(14)71170-2.PubMedCrossRef Topp, M. S., Gokbuget, N., Stein, A. S., Zugmaier, G., O'Brien, S., Bargou, R. C., et al. (2015). Safety and activity of blinatumomab for adult patients with relapsed or refractory B-precursor acute lymphoblastic leukaemia: a multicentre, single-arm, phase 2 study. The Lancet Oncology, 16(1), 57–66. doi:10.​1016/​S1470-2045(14)71170-2.PubMedCrossRef
142.
143.
Zurück zum Zitat Arteaga, C. L., Sliwkowski, M. X., Osborne, C. K., Perez, E. A., Puglisi, F., & Gianni, L. (2012). Treatment of HER2-positive breast cancer: current status and future perspectives. Nature Reviews. Clinical Oncology, 9(1), 16–32. doi:10.1038/nrclinonc.2011.177.CrossRef Arteaga, C. L., Sliwkowski, M. X., Osborne, C. K., Perez, E. A., Puglisi, F., & Gianni, L. (2012). Treatment of HER2-positive breast cancer: current status and future perspectives. Nature Reviews. Clinical Oncology, 9(1), 16–32. doi:10.​1038/​nrclinonc.​2011.​177.CrossRef
146.
Zurück zum Zitat Krop, I. E., Beeram, M., Modi, S., Jones, S. F., Holden, S. N., Yu, W., et al. (2010). Phase I study of trastuzumab-DM1, an HER2 antibody-drug conjugate, given every 3 weeks to patients with HER2-positive metastatic breast cancer. Journal of Clinical Oncology, 28(16), 2698–2704. doi:10.1200/JCO.2009.26.2071.PubMedCrossRef Krop, I. E., Beeram, M., Modi, S., Jones, S. F., Holden, S. N., Yu, W., et al. (2010). Phase I study of trastuzumab-DM1, an HER2 antibody-drug conjugate, given every 3 weeks to patients with HER2-positive metastatic breast cancer. Journal of Clinical Oncology, 28(16), 2698–2704. doi:10.​1200/​JCO.​2009.​26.​2071.PubMedCrossRef
147.
Zurück zum Zitat Krop, I. E., LoRusso, P., Miller, K. D., Modi, S., Yardley, D., Rodriguez, G., et al. (2012). A phase II study of trastuzumab emtansine in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer who were previously treated with trastuzumab, lapatinib, an anthracycline, a taxane, and capecitabine. Journal of Clinical Oncology, 30(26), 3234–3241. doi:10.1200/JCO.2011.40.5902.PubMedCrossRef Krop, I. E., LoRusso, P., Miller, K. D., Modi, S., Yardley, D., Rodriguez, G., et al. (2012). A phase II study of trastuzumab emtansine in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer who were previously treated with trastuzumab, lapatinib, an anthracycline, a taxane, and capecitabine. Journal of Clinical Oncology, 30(26), 3234–3241. doi:10.​1200/​JCO.​2011.​40.​5902.PubMedCrossRef
148.
Zurück zum Zitat Burris 3rd, H. A., Rugo, H. S., Vukelja, S. J., Vogel, C. L., Borson, R. A., Limentani, S., et al. (2011). Phase II study of the antibody drug conjugate trastuzumab-DM1 for the treatment of human epidermal growth factor receptor 2 (HER2)-positive breast cancer after prior HER2-directed therapy. Journal of Clinical Oncology, 29(4), 398–405. doi:10.1200/JCO.2010.29.5865.PubMedCrossRef Burris 3rd, H. A., Rugo, H. S., Vukelja, S. J., Vogel, C. L., Borson, R. A., Limentani, S., et al. (2011). Phase II study of the antibody drug conjugate trastuzumab-DM1 for the treatment of human epidermal growth factor receptor 2 (HER2)-positive breast cancer after prior HER2-directed therapy. Journal of Clinical Oncology, 29(4), 398–405. doi:10.​1200/​JCO.​2010.​29.​5865.PubMedCrossRef
149.
150.
Zurück zum Zitat Krop, I. E., Kim, S. B., Gonzalez-Martin, A., LoRusso, P. M., Ferrero, J. M., Smitt, M., et al. (2014). Trastuzumab emtansine versus treatment of physician's choice for pretreated HER2-positive advanced breast cancer (TH3RESA): a randomised, open-label, phase 3 trial. The Lancet Oncology, 15(7), 689–699. doi:10.1016/S1470-2045(14)70178-0.PubMedCrossRef Krop, I. E., Kim, S. B., Gonzalez-Martin, A., LoRusso, P. M., Ferrero, J. M., Smitt, M., et al. (2014). Trastuzumab emtansine versus treatment of physician's choice for pretreated HER2-positive advanced breast cancer (TH3RESA): a randomised, open-label, phase 3 trial. The Lancet Oncology, 15(7), 689–699. doi:10.​1016/​S1470-2045(14)70178-0.PubMedCrossRef
151.
Zurück zum Zitat Ellis, P. A., Barrios, C. H., Eiermann, W., Toi, M., Im, Y.-H., Conte, P. F., et al. Phase III, randomized study of trastuzumab emtansine (T-DM1){+/−} pertuzumab (P) vs trastuzumab+ taxane (HT) for first-line treatment of HER2-positive MBC: Primary results from the MARIANNE study. In ASCO Annual Meeting Proceedings, 2015 (Vol. 33, pp. 507, Vol. 15_suppl) Ellis, P. A., Barrios, C. H., Eiermann, W., Toi, M., Im, Y.-H., Conte, P. F., et al. Phase III, randomized study of trastuzumab emtansine (T-DM1){+/−} pertuzumab (P) vs trastuzumab+ taxane (HT) for first-line treatment of HER2-positive MBC: Primary results from the MARIANNE study. In ASCO Annual Meeting Proceedings, 2015 (Vol. 33, pp. 507, Vol. 15_suppl)
153.
Zurück zum Zitat Wiedermann, U., Davis, A. B., & Zielinski, C. C. (2013). Vaccination for the prevention and treatment of breast cancer with special focus on Her-2/neu peptide vaccines. Breast Cancer Research and Treatment, 138(1), 1–12. doi:10.1007/s10549-013-2410-8.PubMedCrossRef Wiedermann, U., Davis, A. B., & Zielinski, C. C. (2013). Vaccination for the prevention and treatment of breast cancer with special focus on Her-2/neu peptide vaccines. Breast Cancer Research and Treatment, 138(1), 1–12. doi:10.​1007/​s10549-013-2410-8.PubMedCrossRef
154.
Zurück zum Zitat Wortzel, R. D., Philipps, C., & Schreiber, H. (1983). Multiple tumour-specific antigens expressed on a single tumour cell. Nature, 304(5922), 165–167.PubMedCrossRef Wortzel, R. D., Philipps, C., & Schreiber, H. (1983). Multiple tumour-specific antigens expressed on a single tumour cell. Nature, 304(5922), 165–167.PubMedCrossRef
155.
Zurück zum Zitat Barrow, C., Browning, J., MacGregor, D., Davis, I. D., Sturrock, S., Jungbluth, A. A., et al. (2006). Tumor antigen expression in melanoma varies according to antigen and stage. Clinical Cancer Research, 12(3 Pt 1), 764–771. doi:10.1158/1078-0432.CCR-05-1544.PubMedCrossRef Barrow, C., Browning, J., MacGregor, D., Davis, I. D., Sturrock, S., Jungbluth, A. A., et al. (2006). Tumor antigen expression in melanoma varies according to antigen and stage. Clinical Cancer Research, 12(3 Pt 1), 764–771. doi:10.​1158/​1078-0432.​CCR-05-1544.PubMedCrossRef
156.
Zurück zum Zitat Holmes, J. P., Gates, J. D., Benavides, L. C., Hueman, M. T., Carmichael, M. G., Patil, R., et al. (2008). Optimal dose and schedule of an HER-2/neu (E75) peptide vaccine to prevent breast cancer recurrence: from US Military Cancer Institute Clinical Trials Group Study I-01 and I-02. Cancer, 113(7), 1666–1675. doi:10.1002/cncr.23772.PubMedCrossRef Holmes, J. P., Gates, J. D., Benavides, L. C., Hueman, M. T., Carmichael, M. G., Patil, R., et al. (2008). Optimal dose and schedule of an HER-2/neu (E75) peptide vaccine to prevent breast cancer recurrence: from US Military Cancer Institute Clinical Trials Group Study I-01 and I-02. Cancer, 113(7), 1666–1675. doi:10.​1002/​cncr.​23772.PubMedCrossRef
157.
Zurück zum Zitat Peoples, G. E., Holmes, J. P., Hueman, M. T., Mittendorf, E. A., Amin, A., Khoo, S., et al. (2008). Combined clinical trial results of a HER2/neu (E75) vaccine for the prevention of recurrence in high-risk breast cancer patients: U.S. Military Cancer Institute Clinical Trials Group Study I-01 and I-02. Clinical Cancer Research, 14(3), 797–803. doi:10.1158/1078-0432.CCR-07-1448.PubMedCrossRef Peoples, G. E., Holmes, J. P., Hueman, M. T., Mittendorf, E. A., Amin, A., Khoo, S., et al. (2008). Combined clinical trial results of a HER2/neu (E75) vaccine for the prevention of recurrence in high-risk breast cancer patients: U.S. Military Cancer Institute Clinical Trials Group Study I-01 and I-02. Clinical Cancer Research, 14(3), 797–803. doi:10.​1158/​1078-0432.​CCR-07-1448.PubMedCrossRef
159.
Zurück zum Zitat Hueman, M. T., Stojadinovic, A., Storrer, C. E., Foley, R. J., Gurney, J. M., Shriver, C. D., et al. (2006). Levels of circulating regulatory CD4+CD25+ T cells are decreased in breast cancer patients after vaccination with a HER2/neu peptide (E75) and GM-CSF vaccine. Breast Cancer Research and Treatment, 98(1), 17–29. doi:10.1007/s10549-005-9108-5.PubMedCrossRef Hueman, M. T., Stojadinovic, A., Storrer, C. E., Foley, R. J., Gurney, J. M., Shriver, C. D., et al. (2006). Levels of circulating regulatory CD4+CD25+ T cells are decreased in breast cancer patients after vaccination with a HER2/neu peptide (E75) and GM-CSF vaccine. Breast Cancer Research and Treatment, 98(1), 17–29. doi:10.​1007/​s10549-005-9108-5.PubMedCrossRef
160.
Zurück zum Zitat Hueman, M. T., Stojadinovic, A., Storrer, C. E., Dehqanzada, Z. A., Gurney, J. M., Shriver, C. D., et al. (2007). Analysis of naive and memory CD4 and CD8 T cell populations in breast cancer patients receiving a HER2/neu peptide (E75) and GM-CSF vaccine. Cancer Immunology, Immunotherapy, 56(2), 135–146. doi:10.1007/s00262-006-0188-9.PubMedCrossRef Hueman, M. T., Stojadinovic, A., Storrer, C. E., Dehqanzada, Z. A., Gurney, J. M., Shriver, C. D., et al. (2007). Analysis of naive and memory CD4 and CD8 T cell populations in breast cancer patients receiving a HER2/neu peptide (E75) and GM-CSF vaccine. Cancer Immunology, Immunotherapy, 56(2), 135–146. doi:10.​1007/​s00262-006-0188-9.PubMedCrossRef
161.
Zurück zum Zitat Holmes, J. P., Clifton, G. T., Patil, R., Benavides, L. C., Gates, J. D., Stojadinovic, A., et al. (2011). Use of booster inoculations to sustain the clinical effect of an adjuvant breast cancer vaccine: from US Military Cancer Institute Clinical Trials Group Study I-01 and I-02. Cancer, 117(3), 463–471. doi:10.1002/cncr.25586.PubMedCrossRef Holmes, J. P., Clifton, G. T., Patil, R., Benavides, L. C., Gates, J. D., Stojadinovic, A., et al. (2011). Use of booster inoculations to sustain the clinical effect of an adjuvant breast cancer vaccine: from US Military Cancer Institute Clinical Trials Group Study I-01 and I-02. Cancer, 117(3), 463–471. doi:10.​1002/​cncr.​25586.PubMedCrossRef
162.
Zurück zum Zitat Mittendorf, E. A., Clifton, G. T., Holmes, J. P., Clive, K. S., Patil, R., Benavides, L. C., et al. (2012). Clinical trial results of the HER-2/neu (E75) vaccine to prevent breast cancer recurrence in high-risk patients: from US Military Cancer Institute Clinical Trials Group Study I-01 and I-02. Cancer, 118(10), 2594–2602. doi:10.1002/cncr.26574.PubMedCrossRef Mittendorf, E. A., Clifton, G. T., Holmes, J. P., Clive, K. S., Patil, R., Benavides, L. C., et al. (2012). Clinical trial results of the HER-2/neu (E75) vaccine to prevent breast cancer recurrence in high-risk patients: from US Military Cancer Institute Clinical Trials Group Study I-01 and I-02. Cancer, 118(10), 2594–2602. doi:10.​1002/​cncr.​26574.PubMedCrossRef
163.
Zurück zum Zitat Vreeland, T. J., Clifton, G. T., Hale, D. F., Sears, A., Patil, R., Holmes, J., et al. (2012). Abstract P5-16-02: Final results of the phase I/II trials of the E75 adjuvant breast cancer vaccine. Cancer Res, 72(24 Supplement), P5-16-02-P15-16-02. Vreeland, T. J., Clifton, G. T., Hale, D. F., Sears, A., Patil, R., Holmes, J., et al. (2012). Abstract P5-16-02: Final results of the phase I/II trials of the E75 adjuvant breast cancer vaccine. Cancer Res, 72(24 Supplement), P5-16-02-P15-16-02.
164.
Zurück zum Zitat Mittendorf, E. A., Clifton, G. T., Holmes, J. P., Schneble, E., van Echo, D., Ponniah, S., et al. (2014). Final report of the phase I/II clinical trial of the E75 (nelipepimut-S) vaccine with booster inoculations to prevent disease recurrence in high-risk breast cancer patients. Annals of Oncology, 25(9), 1735–1742. doi:10.1093/annonc/mdu211.PubMedPubMedCentralCrossRef Mittendorf, E. A., Clifton, G. T., Holmes, J. P., Schneble, E., van Echo, D., Ponniah, S., et al. (2014). Final report of the phase I/II clinical trial of the E75 (nelipepimut-S) vaccine with booster inoculations to prevent disease recurrence in high-risk breast cancer patients. Annals of Oncology, 25(9), 1735–1742. doi:10.​1093/​annonc/​mdu211.PubMedPubMedCentralCrossRef
165.
Zurück zum Zitat Carmichael, M. G., Benavides, L. C., Holmes, J. P., Gates, J. D., Mittendorf, E. A., Ponniah, S., et al. (2010). Results of the first phase 1 clinical trial of the HER-2/neu peptide (GP2) vaccine in disease-free breast cancer patients: United States Military Cancer Institute Clinical Trials Group Study I-04. Cancer, 116(2), 292–301. doi:10.1002/cncr.24756.PubMedCrossRef Carmichael, M. G., Benavides, L. C., Holmes, J. P., Gates, J. D., Mittendorf, E. A., Ponniah, S., et al. (2010). Results of the first phase 1 clinical trial of the HER-2/neu peptide (GP2) vaccine in disease-free breast cancer patients: United States Military Cancer Institute Clinical Trials Group Study I-04. Cancer, 116(2), 292–301. doi:10.​1002/​cncr.​24756.PubMedCrossRef
166.
Zurück zum Zitat Trappey, F., Berry, J. S., Vreeland, T. J., Hale, D. F., Sears, A. K., Ponniah, S., et al. 2013 Randomized phase II clinical trial of the anti-HER2 (GP2) vaccine to prevent recurrence in high-risk breast cancer patients: a planned interim analysis. In JOURNAL OF CLINICAL ONCOLOGY, (Vol. 31, Vol. 15): AMER SOC CLINICAL ONCOLOGY 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA Trappey, F., Berry, J. S., Vreeland, T. J., Hale, D. F., Sears, A. K., Ponniah, S., et al. 2013 Randomized phase II clinical trial of the anti-HER2 (GP2) vaccine to prevent recurrence in high-risk breast cancer patients: a planned interim analysis. In JOURNAL OF CLINICAL ONCOLOGY, (Vol. 31, Vol. 15): AMER SOC CLINICAL ONCOLOGY 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
167.
Zurück zum Zitat Clive, K. S., Tyler, J. A., Clifton, G. T., Holmes, J. P., Ponniah, S., Peoples, G. E., et al. (2012). The GP2 peptide: a HER2/neu-based breast cancer vaccine. Journal of Surgical Oncology, 105(5), 452–458. doi:10.1002/jso.21723.PubMedCrossRef Clive, K. S., Tyler, J. A., Clifton, G. T., Holmes, J. P., Ponniah, S., Peoples, G. E., et al. (2012). The GP2 peptide: a HER2/neu-based breast cancer vaccine. Journal of Surgical Oncology, 105(5), 452–458. doi:10.​1002/​jso.​21723.PubMedCrossRef
168.
Zurück zum Zitat Sotiriadou, N. N., Kallinteris, N. L., Gritzapis, A. D., Voutsas, I. F., Papamichail, M., von Hofe, E., et al. (2007). Ii-Key/HER-2/neu(776-790) hybrid peptides induce more effective immunological responses over the native peptide in lymphocyte cultures from patients with HER-2/neu+ tumors. Cancer Immunology, Immunotherapy, 56(5), 601–613. doi:10.1007/s00262-006-0213-z.PubMedCrossRef Sotiriadou, N. N., Kallinteris, N. L., Gritzapis, A. D., Voutsas, I. F., Papamichail, M., von Hofe, E., et al. (2007). Ii-Key/HER-2/neu(776-790) hybrid peptides induce more effective immunological responses over the native peptide in lymphocyte cultures from patients with HER-2/neu+ tumors. Cancer Immunology, Immunotherapy, 56(5), 601–613. doi:10.​1007/​s00262-006-0213-z.PubMedCrossRef
169.
Zurück zum Zitat Holmes, J. P., Benavides, L. C., Gates, J. D., Carmichael, M. G., Hueman, M. T., Mittendorf, E. A., et al. (2008). Results of the first phase I clinical trial of the novel II-key hybrid preventive HER-2/neu peptide (AE37) vaccine. Journal of Clinical Oncology, 26(20), 3426–3433. doi:10.1200/JCO.2007.15.7842.PubMedCrossRef Holmes, J. P., Benavides, L. C., Gates, J. D., Carmichael, M. G., Hueman, M. T., Mittendorf, E. A., et al. (2008). Results of the first phase I clinical trial of the novel II-key hybrid preventive HER-2/neu peptide (AE37) vaccine. Journal of Clinical Oncology, 26(20), 3426–3433. doi:10.​1200/​JCO.​2007.​15.​7842.PubMedCrossRef
170.
Zurück zum Zitat Gates, J. D., Clifton, G. T., Benavides, L. C., Sears, A. K., Carmichael, M. G., Hueman, M. T., et al. (2010). Circulating regulatory T cells (CD4+CD25+FOXP3+) decrease in breast cancer patients after vaccination with a modified MHC class II HER2/neu (AE37) peptide. Vaccine, 28(47), 7476–7482. doi:10.1016/j.vaccine.2010.09.029.PubMedCrossRef Gates, J. D., Clifton, G. T., Benavides, L. C., Sears, A. K., Carmichael, M. G., Hueman, M. T., et al. (2010). Circulating regulatory T cells (CD4+CD25+FOXP3+) decrease in breast cancer patients after vaccination with a modified MHC class II HER2/neu (AE37) peptide. Vaccine, 28(47), 7476–7482. doi:10.​1016/​j.​vaccine.​2010.​09.​029.PubMedCrossRef
171.
172.
Zurück zum Zitat Hale, D., Perez, S., Sears, A., Clifton, G., Vreeland, T., Holmes, J., et al. (2011). P1-13-01: an update of a phase II trial of the HER2 peptide AE37 vaccine in breast cancer patients to prevent recurrence. Cancer Research, 71(24 Supplement), P1-13-01-P11-13-01.CrossRef Hale, D., Perez, S., Sears, A., Clifton, G., Vreeland, T., Holmes, J., et al. (2011). P1-13-01: an update of a phase II trial of the HER2 peptide AE37 vaccine in breast cancer patients to prevent recurrence. Cancer Research, 71(24 Supplement), P1-13-01-P11-13-01.CrossRef
173.
Zurück zum Zitat Mittendorf, E. A., Schneble, E. J., Perez, S. A., Symanowski, R. P., Vreeland, T. J., Berry, J. S., et al. (2014). Primary analysis of the prospective, randomized, single-blinded phase II trial of AE37 vaccine versus GM-CSF alone administered in the adjuvant setting to high-risk breast cancer patients. Journal of Clinical Oncology, 32, 5s.CrossRef Mittendorf, E. A., Schneble, E. J., Perez, S. A., Symanowski, R. P., Vreeland, T. J., Berry, J. S., et al. (2014). Primary analysis of the prospective, randomized, single-blinded phase II trial of AE37 vaccine versus GM-CSF alone administered in the adjuvant setting to high-risk breast cancer patients. Journal of Clinical Oncology, 32, 5s.CrossRef
174.
Zurück zum Zitat Schneble, E. J., Berry, J. S., Trappey, A. F., Vreeland, T. J., Hale, D. F., Sears, A. K., et al. (2013). Vaccine-specific T-cell proliferation in response to a dual peptide cancer vaccine in breast and ovarian cancer patients. Journal for immunotherapy of cancer, 1(1), 1–1.CrossRef Schneble, E. J., Berry, J. S., Trappey, A. F., Vreeland, T. J., Hale, D. F., Sears, A. K., et al. (2013). Vaccine-specific T-cell proliferation in response to a dual peptide cancer vaccine in breast and ovarian cancer patients. Journal for immunotherapy of cancer, 1(1), 1–1.CrossRef
175.
Zurück zum Zitat Miyako, H., Kametani, Y., Katano, I., Ito, R., Tsuda, B., Furukawa, A., et al. (2011). Antitumor effect of new HER2 peptide vaccination based on B cell epitope. Anticancer Research, 31(10), 3361–3368.PubMed Miyako, H., Kametani, Y., Katano, I., Ito, R., Tsuda, B., Furukawa, A., et al. (2011). Antitumor effect of new HER2 peptide vaccination based on B cell epitope. Anticancer Research, 31(10), 3361–3368.PubMed
176.
Zurück zum Zitat Dakappagari, N. K., Douglas, D. B., Triozzi, P. L., Stevens, V. C., & Kaumaya, P. T. (2000). Prevention of mammary tumors with a chimeric HER-2 B-cell epitope peptide vaccine. Cancer Research, 60(14), 3782–3789.PubMed Dakappagari, N. K., Douglas, D. B., Triozzi, P. L., Stevens, V. C., & Kaumaya, P. T. (2000). Prevention of mammary tumors with a chimeric HER-2 B-cell epitope peptide vaccine. Cancer Research, 60(14), 3782–3789.PubMed
177.
Zurück zum Zitat Dakappagari, N. K., Pyles, J., Parihar, R., Carson, W. E., Young, D. C., & Kaumaya, P. T. (2003). A chimeric multi-human epidermal growth factor receptor-2 B cell epitope peptide vaccine mediates superior antitumor responses. Journal of Immunology, 170(8), 4242–4253.CrossRef Dakappagari, N. K., Pyles, J., Parihar, R., Carson, W. E., Young, D. C., & Kaumaya, P. T. (2003). A chimeric multi-human epidermal growth factor receptor-2 B cell epitope peptide vaccine mediates superior antitumor responses. Journal of Immunology, 170(8), 4242–4253.CrossRef
178.
Zurück zum Zitat Kaumaya, P. T., Foy, K. C., Garrett, J., Rawale, S. V., Vicari, D., Thurmond, J. M., et al. (2009). Phase I active immunotherapy with combination of two chimeric, human epidermal growth factor receptor 2, B-cell epitopes fused to a promiscuous T-cell epitope in patients with metastatic and/or recurrent solid tumors. Journal of Clinical Oncology, 27(31), 5270–5277. doi:10.1200/JCO.2009.22.3883.PubMedPubMedCentralCrossRef Kaumaya, P. T., Foy, K. C., Garrett, J., Rawale, S. V., Vicari, D., Thurmond, J. M., et al. (2009). Phase I active immunotherapy with combination of two chimeric, human epidermal growth factor receptor 2, B-cell epitopes fused to a promiscuous T-cell epitope in patients with metastatic and/or recurrent solid tumors. Journal of Clinical Oncology, 27(31), 5270–5277. doi:10.​1200/​JCO.​2009.​22.​3883.PubMedPubMedCentralCrossRef
179.
Zurück zum Zitat Wiedermann, U., Wiltschke, C., Jasinska, J., Kundi, M., Zurbriggen, R., Garner-Spitzer, E., et al. (2010). A virosomal formulated Her-2/neu multi-peptide vaccine induces Her-2/neu-specific immune responses in patients with metastatic breast cancer: a phase I study. Breast Cancer Research and Treatment, 119(3), 673–683.PubMedCrossRef Wiedermann, U., Wiltschke, C., Jasinska, J., Kundi, M., Zurbriggen, R., Garner-Spitzer, E., et al. (2010). A virosomal formulated Her-2/neu multi-peptide vaccine induces Her-2/neu-specific immune responses in patients with metastatic breast cancer: a phase I study. Breast Cancer Research and Treatment, 119(3), 673–683.PubMedCrossRef
181.
Zurück zum Zitat Benavides, L. C., Gates, J. D., Carmichael, M. G., Patil, R., Holmes, J. P., Hueman, M. T., et al. (2009). The impact of HER2/neu expression level on response to the E75 vaccine: from U.S. Military Cancer Institute Clinical Trials Group Study I-01 and I-02. Clinical Cancer Research, 15(8), 2895–2904. doi:10.1158/1078-0432.CCR-08-1126.PubMedCrossRef Benavides, L. C., Gates, J. D., Carmichael, M. G., Patil, R., Holmes, J. P., Hueman, M. T., et al. (2009). The impact of HER2/neu expression level on response to the E75 vaccine: from U.S. Military Cancer Institute Clinical Trials Group Study I-01 and I-02. Clinical Cancer Research, 15(8), 2895–2904. doi:10.​1158/​1078-0432.​CCR-08-1126.PubMedCrossRef
183.
Zurück zum Zitat Patil, R., Clifton, G. T., Litton, J. K., Shumway, N. M., Vreeland, T. J., Berry, J. S., et al. 2013 Safety and efficacy of the HER2-derived GP2 peptide vaccine in combination with trastuzumab for breast cancer patients in the adjuvant setting. In JOURNAL OF CLINICAL ONCOLOGY, (Vol. 31, Vol. 15): AMER SOC CLINICAL ONCOLOGY 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA Patil, R., Clifton, G. T., Litton, J. K., Shumway, N. M., Vreeland, T. J., Berry, J. S., et al. 2013 Safety and efficacy of the HER2-derived GP2 peptide vaccine in combination with trastuzumab for breast cancer patients in the adjuvant setting. In JOURNAL OF CLINICAL ONCOLOGY, (Vol. 31, Vol. 15): AMER SOC CLINICAL ONCOLOGY 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
184.
Zurück zum Zitat Cerullo, V., Diaconu, I., Kangasniemi, L., Rajecki, M., Escutenaire, S., Koski, A., et al. (2011). Immunological effects of low-dose cyclophosphamide in cancer patients treated with oncolytic adenovirus. Molecular Therapy, 19(9), 1737–1746. doi:10.1038/mt.2011.113.PubMedPubMedCentralCrossRef Cerullo, V., Diaconu, I., Kangasniemi, L., Rajecki, M., Escutenaire, S., Koski, A., et al. (2011). Immunological effects of low-dose cyclophosphamide in cancer patients treated with oncolytic adenovirus. Molecular Therapy, 19(9), 1737–1746. doi:10.​1038/​mt.​2011.​113.PubMedPubMedCentralCrossRef
185.
Zurück zum Zitat Demaria, S., Volm, M. D., Shapiro, R. L., Yee, H. T., Oratz, R., Formenti, S. C., et al. (2001). Development of tumor-infiltrating lymphocytes in breast cancer after neoadjuvant paclitaxel chemotherapy. Clinical Cancer Research, 7(10), 3025–3030.PubMed Demaria, S., Volm, M. D., Shapiro, R. L., Yee, H. T., Oratz, R., Formenti, S. C., et al. (2001). Development of tumor-infiltrating lymphocytes in breast cancer after neoadjuvant paclitaxel chemotherapy. Clinical Cancer Research, 7(10), 3025–3030.PubMed
186.
Zurück zum Zitat Emens, L. A., Asquith, J. M., Leatherman, J. M., Kobrin, B. J., Petrik, S., Laiko, M., et al. (2009). Timed sequential treatment with cyclophosphamide, doxorubicin, and an allogeneic granulocyte-macrophage colony-stimulating factor-secreting breast tumor vaccine: a chemotherapy dose-ranging factorial study of safety and immune activation. Journal of Clinical Oncology, 27(35), 5911–5918. doi:10.1200/JCO.2009.23.3494.PubMedPubMedCentralCrossRef Emens, L. A., Asquith, J. M., Leatherman, J. M., Kobrin, B. J., Petrik, S., Laiko, M., et al. (2009). Timed sequential treatment with cyclophosphamide, doxorubicin, and an allogeneic granulocyte-macrophage colony-stimulating factor-secreting breast tumor vaccine: a chemotherapy dose-ranging factorial study of safety and immune activation. Journal of Clinical Oncology, 27(35), 5911–5918. doi:10.​1200/​JCO.​2009.​23.​3494.PubMedPubMedCentralCrossRef
187.
Zurück zum Zitat Chen, G., Gupta, R., Petrik, S., Laiko, M., Leatherman, J. M., Asquith, J. M., et al. (2014). A feasibility study of cyclophosphamide, trastuzumab, and an allogeneic GM-CSF-secreting breast tumor vaccine for HER2+ metastatic breast cancer. Cancer Immunology Research, 2(10), 949–961. doi:10.1158/2326-6066.CIR-14-0058.PubMedPubMedCentralCrossRef Chen, G., Gupta, R., Petrik, S., Laiko, M., Leatherman, J. M., Asquith, J. M., et al. (2014). A feasibility study of cyclophosphamide, trastuzumab, and an allogeneic GM-CSF-secreting breast tumor vaccine for HER2+ metastatic breast cancer. Cancer Immunology Research, 2(10), 949–961. doi:10.​1158/​2326-6066.​CIR-14-0058.PubMedPubMedCentralCrossRef
188.
Zurück zum Zitat Pruitt, S. K., Boczkowski, D., de Rosa, N., Haley, N. R., Morse, M. A., Tyler, D. S., et al. (2011). Enhancement of anti-tumor immunity through local modulation of CTLA-4 and GITR by dendritic cells. European Journal of Immunology, 41(12), 3553–3563. doi:10.1002/eji.201141383.PubMedCrossRef Pruitt, S. K., Boczkowski, D., de Rosa, N., Haley, N. R., Morse, M. A., Tyler, D. S., et al. (2011). Enhancement of anti-tumor immunity through local modulation of CTLA-4 and GITR by dendritic cells. European Journal of Immunology, 41(12), 3553–3563. doi:10.​1002/​eji.​201141383.PubMedCrossRef
189.
Zurück zum Zitat Soliman, H. H., Minton, S. E., Ismail-Khan, R., Han, H. S., Vahanian, N. N., Link, C. J., et al. (2015). Abstract P2-15-04: A phase 1/2 study of Ad. p53 DC vaccine with indoximod immunotherapy in metastatic breast cancer. Cancer Res, 75(9 Supplement), P2-15-04-P12-15-04. Soliman, H. H., Minton, S. E., Ismail-Khan, R., Han, H. S., Vahanian, N. N., Link, C. J., et al. (2015). Abstract P2-15-04: A phase 1/2 study of Ad. p53 DC vaccine with indoximod immunotherapy in metastatic breast cancer. Cancer Res, 75(9 Supplement), P2-15-04-P12-15-04.
190.
Zurück zum Zitat Hamid, O., Schmidt, H., Nissan, A., Ridolfi, L., Aamdal, S., Hansson, J., et al. (2011). A prospective phase II trial exploring the association between tumor microenvironment biomarkers and clinical activity of ipilimumab in advanced melanoma. Journal of Translational Medicine, 9, 204. doi:10.1186/1479-5876-9-204.PubMedPubMedCentralCrossRef Hamid, O., Schmidt, H., Nissan, A., Ridolfi, L., Aamdal, S., Hansson, J., et al. (2011). A prospective phase II trial exploring the association between tumor microenvironment biomarkers and clinical activity of ipilimumab in advanced melanoma. Journal of Translational Medicine, 9, 204. doi:10.​1186/​1479-5876-9-204.PubMedPubMedCentralCrossRef
192.
Zurück zum Zitat Saenger, Y., Magidson, J., Liaw, B., de Moll, E., Harcharik, S., Fu, Y., et al. (2014). Blood mRNA expression profiling predicts survival in patients treated with tremelimumab. Clinical Cancer Research, 20(12), 3310–3318. doi:10.1158/1078-0432.CCR-13-2906.PubMedCrossRef Saenger, Y., Magidson, J., Liaw, B., de Moll, E., Harcharik, S., Fu, Y., et al. (2014). Blood mRNA expression profiling predicts survival in patients treated with tremelimumab. Clinical Cancer Research, 20(12), 3310–3318. doi:10.​1158/​1078-0432.​CCR-13-2906.PubMedCrossRef
193.
Zurück zum Zitat Shahabi, V., Berman, D., Chasalow, S. D., Wang, L., Tsuchihashi, Z., Hu, B., et al. (2013). Gene expression profiling of whole blood in ipilimumab-treated patients for identification of potential biomarkers of immune-related gastrointestinal adverse events. Journal of Translational Medicine, 11, 75. doi:10.1186/1479-5876-11-75.PubMedPubMedCentralCrossRef Shahabi, V., Berman, D., Chasalow, S. D., Wang, L., Tsuchihashi, Z., Hu, B., et al. (2013). Gene expression profiling of whole blood in ipilimumab-treated patients for identification of potential biomarkers of immune-related gastrointestinal adverse events. Journal of Translational Medicine, 11, 75. doi:10.​1186/​1479-5876-11-75.PubMedPubMedCentralCrossRef
194.
Zurück zum Zitat Topalian, S. L., Hodi, F. S., Brahmer, J. R., Gettinger, S. N., Smith, D. C., McDermott, D. F., et al. (2012). Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. The New England Journal of Medicine, 366(26), 2443–2454. doi:10.1056/NEJMoa1200690.PubMedPubMedCentralCrossRef Topalian, S. L., Hodi, F. S., Brahmer, J. R., Gettinger, S. N., Smith, D. C., McDermott, D. F., et al. (2012). Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. The New England Journal of Medicine, 366(26), 2443–2454. doi:10.​1056/​NEJMoa1200690.PubMedPubMedCentralCrossRef
195.
Zurück zum Zitat Grosso, J., Horak, C. E., Inzunza, D., Cardona, D. M., Simon, J. S., Gupta, A. K., et al. 2013 Association of tumor PD-L1 expression and immune biomarkers with clinical activity in patients (pts) with advanced solid tumors treated with nivolumab (anti-PD-1; BMS-936558; ONO-4538). In Journal of Clinical Oncology, (Vol. 31, Vol. 15): AMER SOC CLINICAL ONCOLOGY 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA Grosso, J., Horak, C. E., Inzunza, D., Cardona, D. M., Simon, J. S., Gupta, A. K., et al. 2013 Association of tumor PD-L1 expression and immune biomarkers with clinical activity in patients (pts) with advanced solid tumors treated with nivolumab (anti-PD-1; BMS-936558; ONO-4538). In Journal of Clinical Oncology, (Vol. 31, Vol. 15): AMER SOC CLINICAL ONCOLOGY 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
196.
Zurück zum Zitat Callahan, M. K., Horak, C. E., Curran, M. A., Hollman, T., Schaer, D. A., Yuan, J., et al. 2013 Peripheral and tumor immune correlates in patients with advanced melanoma treated with combination nivolumab (anti-PD-1, BMS-936558, ONO-4538) and ipilimumab. In JOURNAL OF CLINICAL ONCOLOGY, (Vol. 31, Vol. 15): AMER SOC CLINICAL ONCOLOGY 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA Callahan, M. K., Horak, C. E., Curran, M. A., Hollman, T., Schaer, D. A., Yuan, J., et al. 2013 Peripheral and tumor immune correlates in patients with advanced melanoma treated with combination nivolumab (anti-PD-1, BMS-936558, ONO-4538) and ipilimumab. In JOURNAL OF CLINICAL ONCOLOGY, (Vol. 31, Vol. 15): AMER SOC CLINICAL ONCOLOGY 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
197.
Zurück zum Zitat Wolchok, J. D., Kluger, H., Callahan, M. K., Postow, M. A., Rizvi, N. A., Lesokhin, A. M., et al. (2013). Nivolumab plus ipilimumab in advanced melanoma. The New England Journal of Medicine, 369(2), 122–133. doi:10.1056/NEJMoa1302369.PubMedCrossRef Wolchok, J. D., Kluger, H., Callahan, M. K., Postow, M. A., Rizvi, N. A., Lesokhin, A. M., et al. (2013). Nivolumab plus ipilimumab in advanced melanoma. The New England Journal of Medicine, 369(2), 122–133. doi:10.​1056/​NEJMoa1302369.PubMedCrossRef
198.
Zurück zum Zitat Postow, M. A., Cardona, D. M., Taube, J. M., Anders, R. A., Taylor, C. R., Wolchok, J. D., et al. (2014). Peripheral and tumor immune correlates in patients with advanced melanoma treated with nivolumab (anti-PD-1, BMS-936558, ONO-4538) monotherapy or in combination with ipilimumab. Journal of Translational Medicine, 12(Suppl 1), O8.PubMedCentralCrossRef Postow, M. A., Cardona, D. M., Taube, J. M., Anders, R. A., Taylor, C. R., Wolchok, J. D., et al. (2014). Peripheral and tumor immune correlates in patients with advanced melanoma treated with nivolumab (anti-PD-1, BMS-936558, ONO-4538) monotherapy or in combination with ipilimumab. Journal of Translational Medicine, 12(Suppl 1), O8.PubMedCentralCrossRef
199.
Zurück zum Zitat Ku, G. Y., Yuan, J., Page, D. B., Schroeder, S. E., Panageas, K. S., Carvajal, R. D., et al. (2010). Single-institution experience with ipilimumab in advanced melanoma patients in the compassionate use setting. Cancer, 116(7), 1767–1775.PubMedPubMedCentralCrossRef Ku, G. Y., Yuan, J., Page, D. B., Schroeder, S. E., Panageas, K. S., Carvajal, R. D., et al. (2010). Single-institution experience with ipilimumab in advanced melanoma patients in the compassionate use setting. Cancer, 116(7), 1767–1775.PubMedPubMedCentralCrossRef
200.
Zurück zum Zitat Postow, M. A., Yuan, J., Panageas, K., Bogatch, K., Callahan, M., Cheng, M., et al. 2012 Evaluation of the absolute lymphocyte count as a biomarker for melanoma patients treated with the commercially available dose of ipilimumab (3mg/kg). In JOURNAL OF CLINICAL ONCOLOGY, (Vol. 30, Vol. 15): AMER SOC CLINICAL ONCOLOGY 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA Postow, M. A., Yuan, J., Panageas, K., Bogatch, K., Callahan, M., Cheng, M., et al. 2012 Evaluation of the absolute lymphocyte count as a biomarker for melanoma patients treated with the commercially available dose of ipilimumab (3mg/kg). In JOURNAL OF CLINICAL ONCOLOGY, (Vol. 30, Vol. 15): AMER SOC CLINICAL ONCOLOGY 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
201.
Zurück zum Zitat Postow, M. A., Chasalow, S. D., Yuan, J., Kuk, D., Panageas, K. S., Cheng, M., et al. 2013 Pharmacodynamic effect of ipilimumab on absolute lymphocyte count (ALC) and association with overall survival in patients with advanced melanoma. In JOURNAL OF CLINICAL ONCOLOGY, (Vol. 31, Vol. 15): AMER SOC CLINICAL ONCOLOGY 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA Postow, M. A., Chasalow, S. D., Yuan, J., Kuk, D., Panageas, K. S., Cheng, M., et al. 2013 Pharmacodynamic effect of ipilimumab on absolute lymphocyte count (ALC) and association with overall survival in patients with advanced melanoma. In JOURNAL OF CLINICAL ONCOLOGY, (Vol. 31, Vol. 15): AMER SOC CLINICAL ONCOLOGY 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
202.
Zurück zum Zitat Schindler, K., Harmankaya, K., Postow, M. A., Frantal, S., Bello, D., Ariyan, C. E., et al. 2013 Pretreatment levels of absolute and relative eosinophil count to improve overall survival (OS) in patients with metastatic melanoma under treatment with ipilimumab, an anti CTLA-4 antibody. In JOURNAL OF CLINICAL ONCOLOGY, (Vol. 31, Vol. 15): AMER SOC CLINICAL ONCOLOGY 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA Schindler, K., Harmankaya, K., Postow, M. A., Frantal, S., Bello, D., Ariyan, C. E., et al. 2013 Pretreatment levels of absolute and relative eosinophil count to improve overall survival (OS) in patients with metastatic melanoma under treatment with ipilimumab, an anti CTLA-4 antibody. In JOURNAL OF CLINICAL ONCOLOGY, (Vol. 31, Vol. 15): AMER SOC CLINICAL ONCOLOGY 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
203.
Zurück zum Zitat Schindler, K., Harmankaya, K., Kuk, D., Mangana, J., Michielin, O., Hoeller, C., et al. Correlation of absolute and relative eosinophil counts with immune-related adverse events in melanoma patients treated with ipilimumab. In ASCO Annual Meeting Proceedings, 2014 (Vol. 32, pp. 9096, Vol. 15_suppl) Schindler, K., Harmankaya, K., Kuk, D., Mangana, J., Michielin, O., Hoeller, C., et al. Correlation of absolute and relative eosinophil counts with immune-related adverse events in melanoma patients treated with ipilimumab. In ASCO Annual Meeting Proceedings, 2014 (Vol. 32, pp. 9096, Vol. 15_suppl)
204.
Zurück zum Zitat Adams, S., Gray, R. J., Demaria, S., Goldstein, L., Perez, E. A., Shulman, L. N., et al. (2014). Prognostic value of tumor-infiltrating lymphocytes in triple-negative breast cancers from two phase III randomized adjuvant breast cancer trials: ECOG 2197 and ECOG 1199. Journal of Clinical Oncology, 32(27), 2959–2966. doi:10.1200/JCO.2013.55.0491.PubMedPubMedCentralCrossRef Adams, S., Gray, R. J., Demaria, S., Goldstein, L., Perez, E. A., Shulman, L. N., et al. (2014). Prognostic value of tumor-infiltrating lymphocytes in triple-negative breast cancers from two phase III randomized adjuvant breast cancer trials: ECOG 2197 and ECOG 1199. Journal of Clinical Oncology, 32(27), 2959–2966. doi:10.​1200/​JCO.​2013.​55.​0491.PubMedPubMedCentralCrossRef
205.
Zurück zum Zitat Loi, S., Sirtaine, N., Piette, F., Salgado, R., Viale, G., Van Eenoo, F., et al. (2013). Prognostic and predictive value of tumor-infiltrating lymphocytes in a phase III randomized adjuvant breast cancer trial in node-positive breast cancer comparing the addition of docetaxel to doxorubicin with doxorubicin-based chemotherapy: BIG 02-98. Journal of Clinical Oncology, 31(7), 860–867. doi:10.1200/JCO.2011.41.0902.PubMedCrossRef Loi, S., Sirtaine, N., Piette, F., Salgado, R., Viale, G., Van Eenoo, F., et al. (2013). Prognostic and predictive value of tumor-infiltrating lymphocytes in a phase III randomized adjuvant breast cancer trial in node-positive breast cancer comparing the addition of docetaxel to doxorubicin with doxorubicin-based chemotherapy: BIG 02-98. Journal of Clinical Oncology, 31(7), 860–867. doi:10.​1200/​JCO.​2011.​41.​0902.PubMedCrossRef
206.
Zurück zum Zitat Mahmoud, S. M., Paish, E. C., Powe, D. G., Macmillan, R. D., Grainge, M. J., Lee, A. H., et al. (2011). Tumor-infiltrating CD8+ lymphocytes predict clinical outcome in breast cancer. Journal of Clinical Oncology, 29(15), 1949–1955. doi:10.1200/JCO.2010.30.5037.PubMedCrossRef Mahmoud, S. M., Paish, E. C., Powe, D. G., Macmillan, R. D., Grainge, M. J., Lee, A. H., et al. (2011). Tumor-infiltrating CD8+ lymphocytes predict clinical outcome in breast cancer. Journal of Clinical Oncology, 29(15), 1949–1955. doi:10.​1200/​JCO.​2010.​30.​5037.PubMedCrossRef
Metadaten
Titel
Immunotherapy for breast cancer: past, present, and future
verfasst von
Alison Spellman
Shou-Ching Tang
Publikationsdatum
02.12.2016
Verlag
Springer US
Erschienen in
Cancer and Metastasis Reviews / Ausgabe 4/2016
Print ISSN: 0167-7659
Elektronische ISSN: 1573-7233
DOI
https://doi.org/10.1007/s10555-016-9654-9

Weitere Artikel der Ausgabe 4/2016

Cancer and Metastasis Reviews 4/2016 Zur Ausgabe

EditorialNotes

Preface

Umsetzung der POMGAT-Leitlinie läuft

03.05.2024 DCK 2024 Kongressbericht

Seit November 2023 gibt es evidenzbasierte Empfehlungen zum perioperativen Management bei gastrointestinalen Tumoren (POMGAT) auf S3-Niveau. Vieles wird schon entsprechend der Empfehlungen durchgeführt. Wo es im Alltag noch hapert, zeigt eine Umfrage in einem Klinikverbund.

CUP-Syndrom: Künstliche Intelligenz kann Primärtumor finden

30.04.2024 Künstliche Intelligenz Nachrichten

Krebserkrankungen unbekannten Ursprungs (CUP) sind eine diagnostische Herausforderung. KI-Systeme können Pathologen dabei unterstützen, zytologische Bilder zu interpretieren, um den Primärtumor zu lokalisieren.

Sind Frauen die fähigeren Ärzte?

30.04.2024 Gendermedizin Nachrichten

Patienten, die von Ärztinnen behandelt werden, dürfen offenbar auf bessere Therapieergebnisse hoffen als Patienten von Ärzten. Besonders gilt das offenbar für weibliche Kranke, wie eine Studie zeigt.

Adjuvante Immuntherapie verlängert Leben bei RCC

25.04.2024 Nierenkarzinom Nachrichten

Nun gibt es auch Resultate zum Gesamtüberleben: Eine adjuvante Pembrolizumab-Therapie konnte in einer Phase-3-Studie das Leben von Menschen mit Nierenzellkarzinom deutlich verlängern. Die Sterberate war im Vergleich zu Placebo um 38% geringer.

Update Onkologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.