Skip to main content
Erschienen in: Cancer Immunology, Immunotherapy 10/2016

22.08.2016 | Original Article

Immunological evaluation of personalized peptide vaccination for patients with histologically unfavorable carcinoma of unknown primary site

verfasst von: Shinjiro Sakamoto, Shigeru Yutani, Shigeki Shichijo, Michi Morita, Akira Yamada, Kyogo Itoh, Masanori Noguchi

Erschienen in: Cancer Immunology, Immunotherapy | Ausgabe 10/2016

Einloggen, um Zugang zu erhalten

Abstract

The immunological characteristics of carcinoma of unknown primary site (CUP) are not well established due to inclusion of heterogeneous types of metastatic tumors with the absence of any detectable primary site. We evaluated the immune responses in patients with histologically unfavorable CUP during personalized peptide vaccination (PPV). Ten patients with histologically unfavorable CUP who had been treated by PPV after chemotherapy failure were analyzed. In PPV treatment, up to four human leukocyte antigen-matched peptides of a total 31 peptides were selected according to preexisting host immunity before vaccination and administered subcutaneously. Peptides derived from the Lck antigen were most often chosen for use among all patients. CTL responses were increased in 8 of the 10 and 5 of the five patients tested at the end of the first and second PPV cycles, respectively. Increases in humoral responses after vaccination, including IgG, IgG1, IgG3, IgA, and IgM, were observed against not only the vaccinated peptides but also the non-vaccinated peptides. Severe adverse events due to PPV were not observed. Median overall survival was 13.9 months (95 % CI 4.0–22.5 months). PPV activated both cellular and humoral immune responses to short peptides derived from CTL epitopes in the majority of CUP patients. PPV with Lck-derived peptides may be a feasible, new treatment modality for histologically unfavorable CUP patients due to its safety and strong ability to boost immune responses, although its clinical efficacy remains to be investigated in larger-scale trials.
Anhänge
Nur mit Berechtigung zugänglich
Literatur
1.
2.
Zurück zum Zitat Varadhachary GR (2013) New strategies for carcinoma of unknown primary: the role of tissue-of-origin molecular profiling. Clin Cancer Res 19:4027–4033CrossRefPubMed Varadhachary GR (2013) New strategies for carcinoma of unknown primary: the role of tissue-of-origin molecular profiling. Clin Cancer Res 19:4027–4033CrossRefPubMed
3.
Zurück zum Zitat Lee J, Hahn S, Kim DW, Kim J, Kang SN, Rha SY, Lee KB, Kang JH, Park BJ (2013) Evaluation of survival benefits by platinums and taxanes for an unfavourable subset of carcinoma of unknown primary: a systematic review and meta-analysis. Br J Cancer 108:39–48CrossRefPubMed Lee J, Hahn S, Kim DW, Kim J, Kang SN, Rha SY, Lee KB, Kang JH, Park BJ (2013) Evaluation of survival benefits by platinums and taxanes for an unfavourable subset of carcinoma of unknown primary: a systematic review and meta-analysis. Br J Cancer 108:39–48CrossRefPubMed
4.
Zurück zum Zitat Massard C, Loriot Y, Fizazi K (2011) Carcinomas of an unknown primary origin—diagnosis and treatment. Nat Rev Clin Oncol 8:701–710CrossRefPubMed Massard C, Loriot Y, Fizazi K (2011) Carcinomas of an unknown primary origin—diagnosis and treatment. Nat Rev Clin Oncol 8:701–710CrossRefPubMed
5.
Zurück zum Zitat Hainsworth JD, Rubin MS, Spigel DR, Boccia RV, Raby S, Quinn R, Greco FA (2013) Molecular gene expression profiling to predict the tissue of origin and direct site-specific therapy in patients with carcinoma of unknown primary site: a prospective trial of the Sarah Cannon Research Institute. J Clin Oncol 31:217–223CrossRefPubMed Hainsworth JD, Rubin MS, Spigel DR, Boccia RV, Raby S, Quinn R, Greco FA (2013) Molecular gene expression profiling to predict the tissue of origin and direct site-specific therapy in patients with carcinoma of unknown primary site: a prospective trial of the Sarah Cannon Research Institute. J Clin Oncol 31:217–223CrossRefPubMed
6.
Zurück zum Zitat Hainsworth JD, Daugaard G, Lesimple T, Hubner G, Greco FA, Stahl MJ, Büschenfelde CM, Allouache D, Penel N, Knoblauch P, Fizazi KS (2015) Paclitaxel/carboplatin with or without belinostat as empiric first-line treatment for patients with carcinoma of unknown primary site: a randomized, phase 2 trial. Cancer 121:1654–1661CrossRefPubMed Hainsworth JD, Daugaard G, Lesimple T, Hubner G, Greco FA, Stahl MJ, Büschenfelde CM, Allouache D, Penel N, Knoblauch P, Fizazi KS (2015) Paclitaxel/carboplatin with or without belinostat as empiric first-line treatment for patients with carcinoma of unknown primary site: a randomized, phase 2 trial. Cancer 121:1654–1661CrossRefPubMed
7.
Zurück zum Zitat Holtan SG, Steen PD, Foster NR, Erlichman C, Medeiros F, Ames MM, Safgren SL, Graham DL, Behrens RJ, Goetz MP (2012) Gemcitabine and irinotecan as first-line therapy for carcinoma of unknown primary: results of a multicenter phase II trial. PLoS One 7:e39285CrossRefPubMedPubMedCentral Holtan SG, Steen PD, Foster NR, Erlichman C, Medeiros F, Ames MM, Safgren SL, Graham DL, Behrens RJ, Goetz MP (2012) Gemcitabine and irinotecan as first-line therapy for carcinoma of unknown primary: results of a multicenter phase II trial. PLoS One 7:e39285CrossRefPubMedPubMedCentral
8.
Zurück zum Zitat Pentheroudakis G, Golfinopoulos V, Pavlidis N (2007) Switching benchmarks in cancer of unknown primary: from autopsy to microarray. Eur J Cancer 43:2026–2036CrossRefPubMed Pentheroudakis G, Golfinopoulos V, Pavlidis N (2007) Switching benchmarks in cancer of unknown primary: from autopsy to microarray. Eur J Cancer 43:2026–2036CrossRefPubMed
9.
Zurück zum Zitat Busson P, Daya-Grosjean L, Pavlidis N, van de Wouw AJ (2006) The biology of carcinoma of unknown primary site. In: Fizazi K (ed) Carcinoma of an unknown primary site, 1st edn. Taylor & Francis Books LLC, New York, pp 159–174CrossRef Busson P, Daya-Grosjean L, Pavlidis N, van de Wouw AJ (2006) The biology of carcinoma of unknown primary site. In: Fizazi K (ed) Carcinoma of an unknown primary site, 1st edn. Taylor & Francis Books LLC, New York, pp 159–174CrossRef
10.
Zurück zum Zitat Noguchi M, Sasada T, Itoh K (2013) Personalized peptide vaccination: a new approach for advanced cancer as therapeutic cancer vaccine. Cancer Immunol Immunother 62:919–929CrossRefPubMed Noguchi M, Sasada T, Itoh K (2013) Personalized peptide vaccination: a new approach for advanced cancer as therapeutic cancer vaccine. Cancer Immunol Immunother 62:919–929CrossRefPubMed
11.
Zurück zum Zitat Terasaki M, Shibui S, Narita Y, Fujimaki T, Aoki T, Kajiwara K, Sawamura Y, Kurisu K, Mineta T, Yamada A, Itoh K (2011) Phase I trial of a personalized peptide vaccine for patients positive for human leukocyte antigen-A24 with recurrent or progressive glioblastoma multiforme. J Clin Oncol 29:337–344CrossRefPubMed Terasaki M, Shibui S, Narita Y, Fujimaki T, Aoki T, Kajiwara K, Sawamura Y, Kurisu K, Mineta T, Yamada A, Itoh K (2011) Phase I trial of a personalized peptide vaccine for patients positive for human leukocyte antigen-A24 with recurrent or progressive glioblastoma multiforme. J Clin Oncol 29:337–344CrossRefPubMed
12.
Zurück zum Zitat Noguchi M, Matsumoto K, Uemura H, Arai G, Eto M, Naito S, Ohyama C, Nasu Y, Tanaka M, Moriya F, Suekane S, Matsueda S, Komatsu N, Sasada T, Yamada A, Kakuma T, Itoh K (2016) An open-label, randomized phase II trial of personalized peptide vaccination in patients with bladder cancer that progressed after platinum-based chemotherapy. Clin Cancer Res 22:54–60CrossRefPubMed Noguchi M, Matsumoto K, Uemura H, Arai G, Eto M, Naito S, Ohyama C, Nasu Y, Tanaka M, Moriya F, Suekane S, Matsueda S, Komatsu N, Sasada T, Yamada A, Kakuma T, Itoh K (2016) An open-label, randomized phase II trial of personalized peptide vaccination in patients with bladder cancer that progressed after platinum-based chemotherapy. Clin Cancer Res 22:54–60CrossRefPubMed
13.
Zurück zum Zitat Yoshiyama K, Terazaki Y, Matsueda S, Shichijo S, Noguchi M, Yamada A, Mine T, Ioji T, Itoh K, Shirouzu K, Sasada T, Takamori S (2012) Personalized peptide vaccination in patients with refractory non-small cell lung cancer. Int J Oncol 40:1492–1500PubMed Yoshiyama K, Terazaki Y, Matsueda S, Shichijo S, Noguchi M, Yamada A, Mine T, Ioji T, Itoh K, Shirouzu K, Sasada T, Takamori S (2012) Personalized peptide vaccination in patients with refractory non-small cell lung cancer. Int J Oncol 40:1492–1500PubMed
14.
Zurück zum Zitat Komatsu N, Shichijo S, Nakagawa M, Itoh K (2004) New multiplexed flow cytometric assay to measure anti-peptide antibody: a novel tool for monitoring immune responses to peptides used for immunization. Scand J Cin Lab Invest 64:535–545CrossRef Komatsu N, Shichijo S, Nakagawa M, Itoh K (2004) New multiplexed flow cytometric assay to measure anti-peptide antibody: a novel tool for monitoring immune responses to peptides used for immunization. Scand J Cin Lab Invest 64:535–545CrossRef
15.
Zurück zum Zitat Harashima N, Tanaka K, Sasatomi T, Shimizu K, Miyagi Y, Yamada A, Tamura M, Yamana H, Itoh K, Shichijo S (2001) Recognition of the Lck tyrosine kinase as a tumor antigen by cytotoxic T lymphocytes of cancer patients with distant metastases. Eur J Immuno 31:323–332CrossRef Harashima N, Tanaka K, Sasatomi T, Shimizu K, Miyagi Y, Yamada A, Tamura M, Yamana H, Itoh K, Shichijo S (2001) Recognition of the Lck tyrosine kinase as a tumor antigen by cytotoxic T lymphocytes of cancer patients with distant metastases. Eur J Immuno 31:323–332CrossRef
16.
Zurück zum Zitat Amundadottir LT, Leder P (1998) Signal transduction pathways activated and required for mammary carcinogenesis in response to specific oncogenes. Oncogene 16:737–746CrossRefPubMed Amundadottir LT, Leder P (1998) Signal transduction pathways activated and required for mammary carcinogenesis in response to specific oncogenes. Oncogene 16:737–746CrossRefPubMed
17.
Zurück zum Zitat Leung S, Miyamoto NG (1991) Differential expression of two classes of Lck transcripts upon phorbol ester treatment of human leukemic T cells. J Cell Physiol 148:344–352CrossRefPubMed Leung S, Miyamoto NG (1991) Differential expression of two classes of Lck transcripts upon phorbol ester treatment of human leukemic T cells. J Cell Physiol 148:344–352CrossRefPubMed
18.
Zurück zum Zitat Tsuda N, Mochizuki K, Harada M, Sukehiro A, Kawano K, Yamada A, Ushijima K, Sugiyama T, Nishida T, Yamana H, Itoh K, Kamura T (2004) Vaccination with predesignated or evidence-based peptides for patients with recurrent gynecologic cancers. J Immunother 27:60–72CrossRefPubMed Tsuda N, Mochizuki K, Harada M, Sukehiro A, Kawano K, Yamada A, Ushijima K, Sugiyama T, Nishida T, Yamana H, Itoh K, Kamura T (2004) Vaccination with predesignated or evidence-based peptides for patients with recurrent gynecologic cancers. J Immunother 27:60–72CrossRefPubMed
19.
Zurück zum Zitat Mochizuki K, Sato Y, Tsuda N, Shomura H, Sakamoto M, Matsuura K, Ushijima K, Maeda Y, Katagiri K, Yamada A, Todo S, Kamura T, Harada M, Itoh K (2004) Immunological evaluation of vaccination with pre-designated peptides frequently selected as vaccine candidates in an individualized peptide vaccination regimen. Int J Oncol 25:121–131PubMed Mochizuki K, Sato Y, Tsuda N, Shomura H, Sakamoto M, Matsuura K, Ushijima K, Maeda Y, Katagiri K, Yamada A, Todo S, Kamura T, Harada M, Itoh K (2004) Immunological evaluation of vaccination with pre-designated peptides frequently selected as vaccine candidates in an individualized peptide vaccination regimen. Int J Oncol 25:121–131PubMed
20.
Zurück zum Zitat Takahashi R, Ishibashi Y, Hiraoka K, Matsueda S, Kawano K, Kawahara A, Kage M, Ohshima K, Yamanaka R, Shichijo S, Shirouzu K, Itoh K, Sasada T (2013) Phase II study of personalized peptide vaccination for refractory bone and soft tissue sarcoma patients. Cancer Sci 104:1285–1294CrossRefPubMed Takahashi R, Ishibashi Y, Hiraoka K, Matsueda S, Kawano K, Kawahara A, Kage M, Ohshima K, Yamanaka R, Shichijo S, Shirouzu K, Itoh K, Sasada T (2013) Phase II study of personalized peptide vaccination for refractory bone and soft tissue sarcoma patients. Cancer Sci 104:1285–1294CrossRefPubMed
21.
Zurück zum Zitat Kawano K, Tsuda N, Sasada T, Watanabe N, Ushijima K, Yamashita T, Yokomine M, Itoh K, Yamada A, Kamura Y (2014) Feasibility study of personalized peptide vaccination for recurrent ovarian cancer patients. Immunopharmacol Immunotoxicol 36:224–236CrossRefPubMed Kawano K, Tsuda N, Sasada T, Watanabe N, Ushijima K, Yamashita T, Yokomine M, Itoh K, Yamada A, Kamura Y (2014) Feasibility study of personalized peptide vaccination for recurrent ovarian cancer patients. Immunopharmacol Immunotoxicol 36:224–236CrossRefPubMed
Metadaten
Titel
Immunological evaluation of personalized peptide vaccination for patients with histologically unfavorable carcinoma of unknown primary site
verfasst von
Shinjiro Sakamoto
Shigeru Yutani
Shigeki Shichijo
Michi Morita
Akira Yamada
Kyogo Itoh
Masanori Noguchi
Publikationsdatum
22.08.2016
Verlag
Springer Berlin Heidelberg
Erschienen in
Cancer Immunology, Immunotherapy / Ausgabe 10/2016
Print ISSN: 0340-7004
Elektronische ISSN: 1432-0851
DOI
https://doi.org/10.1007/s00262-016-1887-5

Weitere Artikel der Ausgabe 10/2016

Cancer Immunology, Immunotherapy 10/2016 Zur Ausgabe

Update Onkologie

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