Identification of 68 HLA-A24 and -A2-restricted cytotoxic T lymphocyte-inducing peptides derived from 10 common cancer-specific antigens frequently expressed in various solid cancers

IF 4.8 2区医学 Q1 Biochemistry, Genetics and Molecular Biology

Neoplasia Pub Date : 2025-02-11 DOI:10.1016/j.neo.2025.101135

Hiroki Kinoshita , Kazumasa Takenouchi , Nobuo Tsukamoto , Kazunobu Ohnuki , Toshihiro Suzuki , Tetsuya Nakatsura

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引用次数: 0

Abstract

Targeting cancer antigens expressed in cancer cells is necessary to develop cancer-specific immunotherapy. We have performed immunohistochemical analysis of various solid cancer specimens, adding ROBO1, AFP, TGFBI, EphB4, CLDN1, and LAT1 to the previously studied glypican-3 (GPC3), HSP105α, FOXM1, and SPARC, and found that these 10 common cancer antigens are sufficient to cover most solid cancers. These antigens were frequently expressed in various solid cancers but shown to be rarely ex-pressed, with some exceptions, in non-cancerous normal organs adjacent to the cancer. In this study, we predicted 72 and 73 peptides that bind to HLA-A24 and -A2 in silico from the full-length amino acid sequences of these 10 common cancer antigens and immunized each HLA transgenic mouse with a cocktail of synthesized peptides together with the poly I:CLC three times weekly to analyze the antigen-specific immune response. As a result, 68 peptide sequences (30 and 38, respectively) were identified that had higher cytotoxic T lymphocyte (CTL) induction ability than GPC3 298-306 and GPC3 144-152 used in the clinical trials. Furthermore, experiments with cocktail peptide vaccines using mouse models expressing subcutaneous tumors of each antigen showed promising results in terms of safety and efficacy. These peptides identified in this study, derived from 10 common cancer antigens covering all solid cancers, are expected to be clinically applicable as cocktail peptide vaccines.

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来源期刊

Neoplasia 医学-肿瘤学

CiteScore

9.20

自引率

2.10%

发文量

审稿时长

26 days

期刊介绍： Neoplasia publishes the results of novel investigations in all areas of oncology research. The title Neoplasia was chosen to convey the journal’s breadth, which encompasses the traditional disciplines of cancer research as well as emerging fields and interdisciplinary investigations. Neoplasia is interested in studies describing new molecular and genetic findings relating to the neoplastic phenotype and in laboratory and clinical studies demonstrating creative applications of advances in the basic sciences to risk assessment, prognostic indications, detection, diagnosis, and treatment. In addition to regular Research Reports, Neoplasia also publishes Reviews and Meeting Reports. Neoplasia is committed to ensuring a thorough, fair, and rapid review and publication schedule to further its mission of serving both the scientific and clinical communities by disseminating important data and ideas in cancer research.