Phase II study of personalized peptide vaccination for previously treated advanced colorectal cancer.

Abstract

The prognosis of advanced colorectal cancer (aCRC) remains poor, and development of new therapeutic approaches, including immunotherapy, is needed urgently. Herein we report on our phase II study of personalized peptide vaccination (PPV) in 60 previously treated patients with aCRC, who had failed at least one regimen of standard chemotherapy and/or targeted therapy. For PPV, a maximum of four HLA-matched peptides were individually selected from a pool of 31 different peptide candidates based on preexisting host immunity, and administered subcutaneously without severe adverse events. Boosting of IgG and cytotoxic T lymphocyte (CTL) responses specific to the administered peptides was observed in 49% and 63%, respectively, of the patients, who completed the first cycles of six vaccinations. Median overall survival (OS) time was 498 days, with 1- and 2-year survival rates of 53% and 22%, respectively. Multivariate Cox regression analysis of prevaccination factors showed that plasma IL6, IP-10, and BAFF levels were significantly prognostic for OS [hazard ratio (HR), 1.508, P = 0.043; HR, 1.579, P = 0.024; HR, 0.509, P = 0.002, respectively]. In addition, increased peptide-specific CTL responses after vaccination were significantly predictive of favorable OS (HR, 0.231; P = 0.021), suggesting a causal relationship between biologic and clinical efficacy of PPV. On the basis of the safety profile and potential clinical efficacy, we believe that clinical trials of PPV would be warranted for previously treated patients with aCRC.

• Authors: Shiro Kibe, Shigeru Yutani, Satoru Motoyama, Takanobu Nomura, Natsuki Tanaka, Akihiko Kawahara, Tomohiko Yamaguchi, Satoko Matsueda, Nobukazu Komatsu, Masatomo Miura, Yudai Hinai, Satoshi Hattori, Akira Yamada, Masayoshi Kage, Kyogo Itoh, Yoshito Akagi, Tetsuro Sasada
• Journal: Cancer immunology research (Cancer Immunol Res) Vol. 2 Issue 12 Pg. 1154-62 (Dec 2014) ISSN: 2326-6074 [Electronic] United States
• PMID: 25351849 (Publication Type: Clinical Trial, Phase II, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: ©2014 American Association for Cancer Research.

Chemical References

• Cancer Vaccines
• Histocompatibility Antigens
• Immunoglobulin G
• Interleukin-6
• Receptors, Interleukin-6
• Vaccines, Subunit
• C-Reactive Protein

Topics

• Adult
• Aged
• Aged, 80 and over
• C-Reactive Protein (genetics)
• Cancer Vaccines (administration & dosage, adverse effects)
• Colorectal Neoplasms (genetics, immunology, mortality, pathology, therapy)
• Female
• Histocompatibility Antigens (genetics, immunology)
• Humans
• Immunization, Secondary
• Immunoglobulin G (immunology)
• Immunotherapy
• Interleukin-6 (genetics)
• Male
• Middle Aged
• Neoplasm Metastasis
• Neoplasm Staging
• Polymorphism, Single Nucleotide
• Precision Medicine
• Receptors, Interleukin-6 (genetics)
• Retreatment
• T-Lymphocytes, Cytotoxic (immunology, metabolism)
• Treatment Outcome
• Vaccines, Subunit (administration & dosage, adverse effects)