nach oben

Current Treatment Options in Oncology

Erschienen in:

01.12.2018 | Gynecologic Cancers (LA Cantrell, Section Editor)

Review of Immune Therapies Targeting Ovarian Cancer

verfasst von: Cong (Ava) Fan, BS, Jocelyn Reader, PhD, Dana M. Roque, MD

Erschienen in: Current Treatment Options in Oncology | Ausgabe 12/2018

Einloggen, um Zugang zu erhalten

Opinion statement

The rise of immunotherapy is the greatest advance in oncology to occur over the last several years, but applications in gynecologic malignancies lag behind other tumors. The term “immunotherapy” envelops monoclonal antibodies as receptor mediators, including immune checkpoint inhibitors (ICPI), cancer vaccines, and adoptive immunotherapies alone or in combination with other therapeutic approaches. The purpose of this review is to summarize the status of immunotherapy trials in ovarian cancer and to specifically highlight data published in the last 1–2 years.

Ovarian cancer—cancer stat facts [Internet]. [cited 2018 May 21]. Available from: https://seer.cancer.gov/statfacts/html/ovary.html

Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, et al. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer. 2015;136(5):E359–86.CrossRef

Vargas-Hernández VM, Moreno-Eutimio MA, Acosta-Altamirano G, Vargas-Aguilar VM. Management of recurrent epithelial ovarian cancer. Gland Surg. 2014;3(3):198–202.PubMedPubMedCentral

Marth C, Reimer D, Zeimet AG. Front-line therapy of advanced epithelial ovarian cancer: standard treatment. Ann Oncol. 2017;28(suppl_8):viii36–9.CrossRef

Vergote I, Tropé CG, Amant F, Kristensen GB, Ehlen T, Johnson N, et al. Neoadjuvant chemotherapy or primary surgery in stage IIIC or IV ovarian cancer. N Engl J Med. 2010;363(10):943–53.CrossRef

National Comprehensive Cancer Network. Ovarian Cancer v 2.2018.

National Institutes of Health. Surveillance, epidemiology, end results: ovarian cancer.

Chimeric antigen receptor-modified T cells in chronic lymphoid leukemia | NEJM [Internet]. 2011 [cited 2018 May 22]. Available from: https://www.nejm.org/doi/full/10.1056/nejmoa1103849

Forde PM, Chaft JE, Smith KN, Anagnostou V, Cottrell TR, Hellmann MD, et al. Neoadjuvant PD-1 blockade in resectable lung cancer. N Engl J Med. 2018 [cited 2018 May 22]; Available from: https://www.nejm.org/doi/10.1056/NEJMoa1716078?url_ver=Z39.88-2003&rfr_id=ori%3Arid%3Acrossref.org&rfr_dat=cr_pub%3Dwww.ncbi.nlm.nih.gov

10.

Trastuzumab after adjuvant chemotherapy in HER2-Positive breast cancer | NEJM 2005 [Internet]. [cited 2018 May 22]. Available from: https://www.nejm.org/doi/full/10.1056/NEJMoa052306

11.

Clarke B, Tinker AV, Lee C-H, Subramanian S, van de Rijn M, Turbin D, et al. Intraepithelial T cells and prognosis in ovarian carcinoma: novel associations with stage, tumor type, and BRCA1 loss. Mod Pathol. 2009;22(3):393–402.CrossRef

12.

Intratumoral T cells, recurrence, and survival in epithelial ovarian cancer | NEJM [Internet]. 2003 [cited 2018 May 22]. Available from: https://www.nejm.org/doi/10.1056/NEJMoa020177?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%3dwww.ncbi.nlm.nih.gov

13.

Sato E, Olson SH, Ahn J, Bundy B, Nishikawa H, Qian F, et al. Intraepithelial CD8+ tumor-infiltrating lymphocytes and a high CD8+/regulatory T cell ratio are associated with favorable prognosis in ovarian cancer. Proc Natl Acad Sci U S A. 2005;102(51):18538–43.CrossRef

14.

Hwang W-T, Adams SF, Tahirovic E, Hagemann IS, Coukos G. Prognostic significance of tumor-infiltrating T cells in ovarian cancer: a meta-analysis. Gynecol Oncol. 2012;124(2):192–8.CrossRef

15.

Intlekofer AM, Thompson CB. At the bench: preclinical rationale for CTLA-4 and PD-1 blockade as cancer immunotherapy. J Leukoc Biol. 2013;94(1):25–39.CrossRef

16.

Mocellin S, Benna C, Pilati P. Coinhibitory molecules in cancer biology and therapy. Cytokine Growth Factor Rev. 2013;24(2):147–61.CrossRef

17.

Fife BT, Bluestone JA. Control of peripheral T cell tolerance and autoimmunity via the CTLA-4 and PD-1 pathways. Immunol Rev. 2008;224:166–82.CrossRef

18.

Krummel MF, Allison JP. Pillars article: CD28 and CTLA-4 have opposing effects on the response of T cells to stimulation. The Journal of Experimental Medicine. 1995. 182: 459–465. J Immunol. 2011;187(7):3459–65.PubMed

19.

Buchbinder EI, Desai A. CTLA-4 and PD-1 pathways: similarities, differences, and implications of their inhibition. Am J Clin Oncol. 2016;39(1):98–106.CrossRef

20.

Pardoll DM. The blockade of immune checkpoints in cancer immunotherapy. Nat Rev Cancer. 2012;12(4):252–64.CrossRef

21.

Fessas P, Lee H, Ikemizu S, Janowitz T. A molecular and preclinical comparison of the PD-1-targeted T-cell checkpoint inhibitors nivolumab and pembrolizumab. Semin Oncol. 2017;44(2):136–40.CrossRef

22.

•• Disis ML, Patel MR, Pant S, Hamilton EP, Lockhart AC, Kelly K, et al. Avelumab (MSB0010718C; anti-PD-L1) in patients with recurrent/refractory ovarian cancer from the JAVELIN Solid Tumor phase Ib trial: safety and clinical activity. JCO. 2016;34(15_suppl):5533 Available from: http://ascopubs.org/doi/abs/10.1200/JCO.2016.34.15_suppl.5533. A preliminary analysis for trial of avelumab in patients with recurrent or refractory ovarian cancer. Responses for patients that were PD-L1+ were compared with PD-L1- expression.CrossRef

23.•

Phase II study of ipilimumab monotherapy in recurrent platinum-sensitive ovarian cancer—study results - ClinicalTrials.gov [Internet]. [cited 2018 Mar 28]. Available from: https://clinicaltrials.gov/ct2/show/results/NCT01611558. A trial to investigate the overall response and adverse events related to ipilimumab as a monotherapy for recurrent ovarian cancer.

24.

Brahmer JR, Lacchetti C, Schneider BJ, Atkins MB, Brassil KJ, Caterino JM, et al. Management of immune-related adverse events in patients treated with immune checkpoint inhibitor therapy: American Society of Clinical Oncology Clinical Practice Guideline. J Clin Oncol. 2018;14:JCO2017776385.

25.

Safety and activity of anti-PD-L1 antibody in patients with advanced cancer | NEJM [Internet]. 2012 [cited 2018 May 25]. Available from: https://www.nejm.org/doi/full/10.1056/nejmoa1200694

26.

Niraparib in combination with pembrolizumab in patients with triple-negative breast cancer or ovarian cancer - full text view - ClinicalTrials.gov [Internet]. [cited 2018 Mar 26]. Available from: https://clinicaltrials.gov/ct2/show/NCT02657889

27.

PEMBRO with chemo in neo adj treatment of ovarian cancer - full text view - ClinicalTrials.gov [Internet]. [cited 2018 Jun 12]. Available from: https://clinicaltrials.gov/ct2/show/NCT03275506

28.

A phase II study of nivolumab/bevacizumab - full text view - ClinicalTrials.gov [Internet]. [cited 2018 Jun 12]. Available from: https://clinicaltrials.gov/ct2/show/NCT02873962

29.

A study in ovarian cancer patients evaluating rucaparib and nivolumab as maintenance treatment following response to front-line platinum-based chemotherapy - full text view - ClinicalTrials.gov [Internet]. [cited 2018 Jun 12]. Available from: https://clinicaltrials.gov/ct2/show/NCT03522246

30.

ATALANTE: atezolizumab vs placebo phase III study in late relapse ovarian cancer treated with chemotherapy + bevacizumab - full text view - ClinicalTrials.gov [Internet]. [cited 2018 Jun 12]. Available from: https://clinicaltrials.gov/ct2/show/NCT02891824

31.

Lee J-M, Cimino-Mathews A, Peer CJ, Zimmer A, Lipkowitz S, Annunziata CM, et al. Safety and clinical activity of the programmed death-ligand 1 inhibitor durvalumab in combination with poly (ADP-ribose) polymerase inhibitor olaparib or vascular endothelial growth factor receptor 1–3 inhibitor cediranib in women’s cancers: a dose-escalation, phase I study. JCO. 2017;35(19):2193–202.CrossRef

32.

A Study of atezolizumab versus placebo in combination with paclitaxel, carboplatin, and bevacizumab in participants with newly-diagnosed stage iii or stage iv ovarian, fallopian tube, or primary peritoneal cancer - full text view - ClinicalTrials.gov [Internet]. [cited 2018 Mar 26]. Available from: https://clinicaltrials.gov/ct2/show/NCT03038100

33.

Le DT, Uram JN, Wang H, Bartlett BR, Kemberling H, Eyring AD, et al. PD-1 blockade in tumors with mismatch-repair deficiency. N Engl J Med. 2015;372(26):2509–20.CrossRef

34.

Howitt BE, Strickland KC, Sholl LM, Rodig S, Ritterhouse LL, Chowdhury D, et al. Clear cell ovarian cancers with microsatellite instability: a unique subset of ovarian cancers with increased tumor-infiltrating lymphocytes and PD-1/PD-L1 expression. Oncoimmunology [Internet]. 2017 Jan 6 [cited 2018 Apr 2];6(2). Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5353914/

35.

Strickland KC, Howitt BE, Shukla SA, Rodig S, Ritterhouse LL, Liu JF, et al. Association and prognostic significance of BRCA1/2-mutation status with neoantigen load, number of tumor-infiltrating lymphocytes and expression of PD-1/PD-L1 in high grade serous ovarian cancer. Oncotarget. 2016;7(12):13587–98.CrossRef

36.

Bellone S, Buza N, Choi J, Zammataro L, Gay L, Elvin J, et al. Exceptional response to pembrolizumab in a metastatic, chemotherapy/radiation-resistant ovarian cancer patient harboring a PD-L1-genetic rearrangement. Clinical Cancer Research [Internet]. 2018 Jan 19 [cited 2018 Jun 6]; Available from: http://clincancerres.aacrjournals.org/lookup/doi/10.1158/1078-0432.CCR-17-1805

37.

Olaparib, durvalumab, and tremelimumab in treating patients with recurrent or refractory ovarian, fallopian tube or primary peritoneal cancer with BRCA1 or BRCA2 mutation - full text view - ClinicalTrials.gov [Internet]. [cited 2018 Jun 12]. Available from: https://clinicaltrials.gov/ct2/show/NCT02953457

38.

Pembrolizumab in treating participants with metastatic, recurrent or locally advanced cancer and genomic instability - full text view - ClinicalTrials.gov [Internet]. [cited 2018 Jun 12]. Available from: https://clinicaltrials.gov/ct2/show/NCT03428802

39.

Guo C, Manjili MH, Subjeck JR, Sarkar D, Fisher PB, Wang X-Y. Therapeutic cancer vaccines: past, present, and future. Adv Cancer Res. 2013;119:421–75.CrossRef

40.

Senzer N, Barve M, Kuhn J, Melnyk A, Beitsch P, Lazar M, et al. Phase I trial of “bi-shRNAifurin/GMCSF DNA/autologous tumor cell” vaccine (FANG) in advanced cancer. Mol Ther. 2012;20(3):679–86 Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3293620/.CrossRef

41.

Manning L, Barve M, Wallraven G, Kumar P, Taquet N, Bognar E, et al. Assessment of low dose Vigil® engineered autologous tumor cell (EATC) immunotherapy in patients with advanced solid tumors. Clin Oncol. 2017;2:4.

42.

Trial of Adjuvant FANG™ vaccine for high risk stage III/IV ovarian cancer - full text view - ClinicalTrials.gov [Internet]. [cited 2018 Jun 25]. Available from: https://clinicaltrials.gov/ct2/show/NCT01309230

43.

Phase 2 trial of maintenance vigil for high risk stage IIIb-IV ovarian cancer - full text view - ClinicalTrials.gov [Internet]. [cited 2018 Jun 25]. Available from: https://clinicaltrials.gov/ct2/show/NCT02346747

44.

Vreeland TJ, Litton JK, Qiao N, Philips AV, Alatrash G, Hale DF, et al. Phase Ib trial of folate binding protein (FBP)-derived peptide vaccines, E39 and an attenuated version, E39’: an analysis of safety and immune response. Clin Immunol. 2018; Available from: http://www.sciencedirect.com/science/article/pii/S1521661617308653.

44.••

Kalli KR, Block MS, Kasi PM, Erskine CL, Hobday TJ, Dietz A, et al. Folate receptor alpha peptide vaccine generates immunity in breast and ovarian cancer patients. Clin Cancer Res. 2018. A phase I study that demonstrates that generation of an immune response to folate receptor vaccination occurs in a large number of patients in clinical remission and remains detectable at 1 year.

46.

PH3 study of mirvetuximab soravtansine vs investigator’s choice of chemotherapy in women with Fra+ Adv. EOC, primary peritoneal or fallopian tube cancer - full text view - ClinicalTrials.gov [Internet]. [cited 2018 Jun 25]. Available from: https://clinicaltrials.gov/ct2/show/NCT02631876

47.

Altwerger G, Bonazzoli E, Bellone S. In Vitro and in vivo activity of IMGN853, an antibody–drug conjugate targeting folate receptor alpha linked to DM4, in biologically aggressive endometrial cancers. Mol Cancer Ther. 2018; Available from: http://mct.aacrjournals.org/content/17/5/1003.long.

48.

Ab O, Whiteman KR, Bartle L. IMGN853, a folate receptor-α (FRα)–targeting antibody–drug conjugate, exhibits potent targeted antitumor activity against FRα-expressing tumors. Mol Cancer Ther. 2015; Available from: http://mct.aacrjournals.org/content/14/7/1605.long.

49.

Cancer Genome Atlas Research Network. Integrated genomic analyses of ovarian carcinoma. Nature. 2011;474(7353):609–15.CrossRef

50.

Odunsi K. Immunotherapy in ovarian cancer. Ann Oncol. 2017;28(suppl_8):viii1–7 Available from: https://academic.oup.com/annonc/article/28/suppl_8/viii1/4693810.CrossRef

51.

Battaglia A, Fossati M, Buzzonetti A, Scambia G, Fattorossi A. A robust immune system conditions the response to abagovomab (anti-idiotypic monoclonal antibody mimicking the CA125 protein) vaccination in ovarian cancer patients. Immunol Lett. 2017;191:35–9.CrossRef

52.

• Hardwick NR, Frankel P, Ruel C, Kilpatrick J, Tsai W, Kos F, et al. p53-reactive T cells are associated with clinical benefit in patients with platinum-resistant epithelial ovarian cancer after treatment with a p53 vaccine and gemcitabine chemotherapy. Clin Cancer Res. 2018;24(6):1315–25 Available from: http://clincancerres.aacrjournals.org.proxy-hs.researchport.umd.edu/content/24/6/1315. A phase I trial to demonstrate that response to p53 vaccination in conjunction with cytotoxic chemotherapy correlates with longer PFS.CrossRef

53.

Mittica G, Capellero S, Genta S, Cagnazzo C, Aglietta M, Sangiolo D, et al. Adoptive immunotherapy against ovarian cancer. J Ovarian Res. 2016;9 Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4869278/.

54.

Krishnan V, Berek JS, Dorigo O. Immunotherapy in ovarian cancer. Curr Probl Cancer. 2017;41(1):48–63.CrossRef

55.

Uppendahl LD, Dahl CM, Miller JS, Felices M, Geller MA. Natural killer cell-based immunotherapy in gynecologic malignancy: a review. Front Immunol. 2018;8 Available from: https://www.frontiersin.org/articles/10.3389/fimmu.2017.01825/full.

56.

Imai K, Matsuyama S, Miyake S, Suga K, Nakachi K. Natural cytotoxic activity of peripheral-blood lymphocytes and cancer incidence: an 11-year follow-up study of a general population. Lancet. 2000;356(9244):1795–9.CrossRef

57.

Yang Y, Lim O, Kim TM, Ahn Y-O, Choi H, Chung H, et al. Phase I study of random healthy donor-derived allogeneic natural killer cell therapy in patients with malignant lymphoma or advanced solid tumors. Cancer Immunol Res. 2016;4(3):215–24.CrossRef

58.

Eguizabal C, Zenarruzabeitia O, Monge J, Santos S, Vesga MA, Maruri N, et al. Natural killer cells for cancer immunotherapy: pluripotent stem cells-derived NK cells as an immunotherapeutic perspective. Front Immunol. 2014;5:439.CrossRef

59.

Klapdor R, Wang S, Hacker U, Büning H, Morgan M, Dörk T, et al. Improved Killing of ovarian cancer stem cells by combining a novel chimeric antigen receptor-based immunotherapy and chemotherapy. Hum Gene Ther. 2017;28(10):886–96.CrossRef

60.

Martín-Antonio B, Suñe G, Perez-Amill L, Castella M, Urbano-Ispizua A. Natural killer cells: angels and devils for immunotherapy. Int J Mol Sci. 2017;29:18(9).

61.

Liu J, Li H, Cao S, Zhang X, Yu J, Qi J, et al. Maintenance therapy with autologous cytokine-induced killer cells in patients with advanced epithelial ovarian cancer after first-line treatment. J Immunother. 2014;37(2):115–22.CrossRef

62.

Zhang Z, Wang L, Luo Z, Zhao X, Huang J, Li H, et al. Efficacy and safety of cord blood-derived cytokine-induced killer cells in treatment of patients with malignancies. Cytotherapy. 2015;17(8):1130–8.CrossRef

63.

Zhang C, Zhang Z, Wang L, Han J, Li F, Shen C, et al. Pseudomonas aeruginosa-mannose sensitive hemagglutinin injection treated cytokine-induced killer cells combined with chemotherapy in the treatment of malignancies. Int Immunopharmacol. 2017;51:57–65.CrossRef

64.

Rodriguez-Garcia A, Minutolo NG, Robinson JM, Powell DJ. T cell target antigens across major gynecologic cancers. Gynecol Oncol. 2017;145(3):426–35.CrossRef

65.

Andersen R, Donia M, Westergaard MCW, Pedersen M, Hansen M, Svane IM. Tumor infiltrating lymphocyte therapy for ovarian cancer and renal cell carcinoma. Hum Vaccin Immunother. 2015;11(12):2790–5.CrossRef

65.•

Deniger DC, Pasetto A, Robbins PF, Gartner JJ, Prickett TD, Paria BC, et al. T-cell responses to TP53 “hotspot” mutations and unique neoantigens expressed by human ovarian cancers. Clin Cancer Res. 2018. In this paper, TILs from ovarian cancer patients were found to have specificity to mutated neoantigens and that these T cells could be used for adoptive cell therapy. TP53 “hotspot” reactive T cells were also found and these cells could recognize a broad range of tumor types in unrelated individuals.

67.

Bobisse S, Genolet R, Roberti A, Tanyi JL, Racle J, Stevenson BJ, et al. Sensitive and frequent identification of high avidity neo-epitope specific CD8+ T cells in immunotherapy-naive ovarian cancer. Nat Commun. 2018. 1092;9(1):15.

68.

Pedersen M, Westergaard M, Nielsen M, Borch TH, Poulsen LG, Hendel H, et al. 1145PDAdoptive cell therapy with tumor-infiltrating lymphocytes for patients with metastatic ovarian cancer: a pilot study. Ann Oncol. 2017;28(suppl_5) Available from: https://academic.oup.com/annonc/article/28/suppl_5/mdx376.010/4109224.

69.

Fishman MN, Thompson JA, Pennock GK, Gonzalez R, Diez LM, Daud AI, et al. Phase I trial of ALT-801, an interleukin-2/T cell receptor fusion protein targeting p53 (aa264-272)/HLA-A*0201 complex, in patients with advanced malignancies. Clin Cancer Res. 2011;17(24):7765–75.CrossRef

70.

Zhu X, Cai H, Zhao L, Ning L, Lang J, Zhu X, et al. CAR-T cell therapy in ovarian cancer: from the bench to the bedside. Oncotarget. 2017;8(38):64607–21.PubMedPubMedCentral

71.

Tanyi JL, Haas AR, Beatty GL, Stashwick CJ, O’Hara MH, Morgan MA, et al. Anti-mesothelin chimeric antigen receptor T cells in patients with epithelial ovarian cancer. JCO. 2016;34(15_suppl):5511.CrossRef

72.

Lanitis E, Dangaj D, Hagemann IS, Song D-G, Best A, Sandaltzopoulos R, et al. Primary human ovarian epithelial cancer cells broadly express HER2 at immunologically-detectable levels. PLoS ONE. 2012;7(11):e49829.CrossRef

73.

Tanyi JL, Stashwick C, Plesa G, Morgan MA, Porter D, Maus MV, et al. Possible compartmental cytokine release syndrome in a patient with recurrent ovarian cancer after treatment with mesothelin-targeted CAR-T cells. J Immunother. 2017;40(3):104–7.CrossRef

Titel: Review of Immune Therapies Targeting Ovarian Cancer
verfasst von: Cong (Ava) Fan, BS
Jocelyn Reader, PhD
Dana M. Roque, MD
Publikationsdatum: 01.12.2018
Verlag: Springer US
Erschienen in: Current Treatment Options in Oncology / Ausgabe 12/2018
Print ISSN: 1527-2729
Elektronische ISSN: 1534-6277
DOI: https://doi.org/10.1007/s11864-018-0584-3

Neu im Fachgebiet Onkologie

24.04.2024 | DGIM 2024 | Nachrichten

Springer Medizin

Review of Immune Therapies Targeting Ovarian Cancer

Opinion statement

Neu im Fachgebiet Onkologie

Bei Senioren mit Prostatakarzinom auf Anämie achten!

ICI-Therapie in der Schwangerschaft wird gut toleriert

Krebspatienten impfen: Was? Wen? Und wann nicht?

Müde im Alter? Auch an die Nebenniere denken

Update Onkologie

Springer Medizin

Opinion statement

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 12/2018

Radiation-Related Alterations of Taste Function in Patients With Head and Neck Cancer: a Systematic Review

Is There Value in Molecular Profiling of Soft-Tissue Sarcoma?

Minimal Residual Disease in Indolent Lymphomas: A Critical Assessment

Diagnosis and Treatment of Myxoid Liposarcomas: Histology Matters

Capecitabine Versus Continuous Infusion Fluorouracil for the Treatment of Advanced or Metastatic Colorectal Cancer: a Meta-analysis

Window Studies in Squamous Cell Carcinoma of the Head and Neck: Values and Limits

Neu im Fachgebiet Onkologie

Bei Senioren mit Prostatakarzinom auf Anämie achten!

ICI-Therapie in der Schwangerschaft wird gut toleriert

Krebspatienten impfen: Was? Wen? Und wann nicht?

Müde im Alter? Auch an die Nebenniere denken

Update Onkologie