IgG response to MHC class I epitope peptides is a quantitative predictive biomarker in the early course of treatment of colorectal cancer using therapeutic peptides

Shinsuke Kanekiyo, Shoichi Hazama, Hiroko Takenouchi, Masao Nakajima, Yoshitaro Shindo, Hiroto MATSuI, Yukio Tokumitsu, Shinobu Tomochika, Ryouichi Tsunedomi, Yoshihiro Tokuhisa, Michihisa Iida, Kazuhiko Sakamoto, Nobuaki SuzukI, Shigeru Takeda, Shigeru Yamamoto, Shigefumi Yoshino, Kiyotaka Okuno, Keiko Udaka, Yutaka Kawakami, Satoko MatsuedaKyogo Ito, Hiroaki Nagano

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3 Citations (Scopus)

Abstract

Cancer vaccines have been developed as a new therapeutic approach, however, their clinical benefit remains limited. We previously performed a phase II study for advanced colorectal cancer (CRC) using five human leukocyte antigen (HLA-A*24:02)-restricted peptides derived from kinase of the outer chloroplast membrane 1, translocase of outer mitochondrial membrane 34 (TOMM34), ring finger protein 43 (RNF43), vascular endothelial growth factor receptor 1 (VEGFR1) and VEGFR2. In the present study the relationship between overall survival (OS) and several biomarkers, including cytotoxic T lymphocyte (CTL) and immunoglobulin G (IgG) responses to these five peptides, was investigated. In 89 advanced CRC patients treated with a combination therapy consisting of these five peptides and oxaliplatin-based chemotherapy, plasma was collected before and after 3 months of vaccine administration. IgGs reactive to each of the five peptides were assessed using the multiplex bead suspension Luminex system. Antigen-specific T-cell responses were estimated by enzyme-linked immunoSpot assay. Plasma levels of TOMM34 IgG (P<0.001), RNF43 IgG (P<0.001) and VEGFR2 IgG (P<0.001) were significantly increased after vaccination and stronger VEGFR2 IgG responses correlated significantly with OS in HLA-matched patients (P=0.034). CTL responses to VEGFR1 and VEGFR2 were also significantly increased in the HLA-matched group (P=0.049 and P<0.001, respectively). However, increased CTL response did not correlate with OS. Multivariate analysis indicated that IgG responses to VEGFR2 were the most significant predictor for OS in the HLA-A*24:02-matched group (P=0.04). Our findings indicated that VEGFR2 IgG responses may be an important immunological biomarker in the early course of treatment for CRC patients treated with therapeutic epitope peptides.

Original languageEnglish
Pages (from-to)2385-2392
Number of pages8
JournalOncology Reports
Volume39
Issue number5
DOIs
Publication statusPublished - 2018 May 1

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Keywords

  • CTL
  • Epitope peptide
  • IgG
  • Immunological biomarker
  • Overall survival

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Kanekiyo, S., Hazama, S., Takenouchi, H., Nakajima, M., Shindo, Y., MATSuI, H., Tokumitsu, Y., Tomochika, S., Tsunedomi, R., Tokuhisa, Y., Iida, M., Sakamoto, K., SuzukI, N., Takeda, S., Yamamoto, S., Yoshino, S., Okuno, K., Udaka, K., Kawakami, Y., ... Nagano, H. (2018). IgG response to MHC class I epitope peptides is a quantitative predictive biomarker in the early course of treatment of colorectal cancer using therapeutic peptides. Oncology Reports, 39(5), 2385-2392. https://doi.org/10.3892/or.2018.6288