Abstract 7248: Expression profiles of 10 common cancer-specific antigens collected for the development of cancer vaccines and T cell therapies applicable to most solid cancer patients
Authors: Tetsuya Nakatsura, Kazumasa Takenouchi, Jun Kataoka, Yusuke Ito, Sae Kikuchi, Hiroki Kinoshita, Kazunobu Ohnuki, Toshihiro Suzuki, Nobuo Tsukamoto
Journal: Cancer Research (2025)

Abstract We clinical trialed a peptide vaccine derived from the cancer-specific antigen, glypican-3 (GPC3). There have been cases of multiple patients with advanced cancer who responded to the peptide vaccine after just a few doses, and seven patients with refractory pediatric cancer have survived for 10 years without a recurrence, so the peptide vaccine is also expected to be effective in preventing recurrence. On the other hand, we have also seen several cases of GPC3 expression negative cancer recurrence, revealing the limitations of peptide vaccines with a single antigen. To overcome the heterogeneity of individual cancers and apply the antibody to a wide range of solid cancer patients, we collected 10 common cancer-specific antigens, such as GPC3. In this study, we performed immunohistochemical analysis of various solid cancer specimens using antibodies against ROBO1, TGFBI, AFP, EphB4, CLDN1, and LAT1 in addition to GPC3, HSP105α, FOXM1, and SPARC, which we have previously studied. These antigens were frequently expressed in various solid cancers but shown to be rarely expressed, with some exceptions, in non-cancerous normal organs adjacent to the cancer. Even if a normal cell expresses an antigen protein, if the cell does not express HLA class I on its cell membrane, it can escape attack by cytotoxic T lymphocytes (CTL). Many non-cancerous normal cells, including hepatocytes that express HSP105α and pancreatic acinar cells that express CLDN1, do not express or only weakly express HLA class I, and it has been determined that the risk of adverse events from CTLs induced by vaccines containing these antigens or from T cell receptor (TCR)-engineered T cell therapy is low. In our other study, we have identified many peptides derived from these 10 common cancer-specific antigens with higher CTL induction capacity than the GPC3 peptide used in the clinical trial. We are currently developing peptide vaccines and mRNA vaccines. Identifying many TCRs that react to peptides and developing TCR-T cell therapy is also possible. For CTLs to be effective, HLA class I must be expressed on the surface of cancer cells. It was revealed that most solid cancers, except for lung adenocarcinoma and pediatric cancer, frequently express HLA class I on the cell membrane. In addition, it was revealed that the cell membrane antigens EphB4, CLDN1, and LAT1 are frequently expressed in various solid cancers. CAR-T cell therapy targeting these antigens may be a savior for many solid cancer patients. In this study, we clarified the expression profiles of 10 common cancer-specific antigens collected to develop cancer vaccines and T cell therapies that can be applied to most solid tumor patients. We will continue to develop cancer immunotherapies that target these multiple common cancer-specific antigens. Citation Format: Tetsuya Nakatsura, Kazumasa Takenouchi, Jun Kataoka, Yusuke Ito, Sae Kikuchi, Hiroki Kinoshita, Kazunobu Ohnuki, Toshihiro Suzuki, Nobuo Tsukamoto. Expression profiles of 10 common cancer-specific antigens collected for the development of cancer vaccines and T cell therapies applicable to most solid cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 7248.