Abstract 5010: Development of a universal cancer vaccine using common cancer antigens cocktail that targets various cancer patients and overcomes the heterogeneity of individual cancer
Authors: Tetsuya Nakatsura, Kazumasa Takenouchi, Hiroki Kinoshita, Nobuo Tsukamoto, Kazunobu Ohnuki, Toshihiro Suzuki
Journal: Cancer Research (2024)

Abstract In clinical trials of the glypican-3 (GPC3)-derived peptide vaccine targeting hepatocellular carcinoma (HCC), hepatoblastoma, etc., peptide-specific CTL were detected in many patients. There have been some partial response advanced cancer cases, and it is expected to be effective in prolonging the prognosis after HCC surgery. Five children with refractory hepatoblastoma who had repeated relapses and remissions are all surviving for more than 9 years without relapse by only peptide vaccine therapy. On the other hand, several patients have experienced recurrence of hepatocellular carcinoma that does not express GPC3 despite the detection of a large number of peptide-specific CTLs in the blood after administration of peptide vaccines. GPC3 is highly expressed in many hepatocellular carcinomas, but there are GPC3-negative cancer cells, so it is difficult to prevent recurrence of hepatocellular carcinoma with a single type of GPC3 peptide vaccine. In other words, to cure cancer, it is necessary to combine multiple common cancer antigens. Through immunohistochemical analysis, we identified 10 common cancer antigens, including GPC3, that are frequently expressed in various solid cancers but rarely expressed in normal tissues. Five of these antigens are membrane protein antigens, and we have confirmed that at least one of these antigens, and often more than one, is expressed in many cancers investigated. We synthesized peptides predicted to be presented at HLA-A*24:02 or HLA-A*02:01 from the full-length amino acid sequences of 10 types of common cancer antigen proteins. These peptide vaccines were administered to HLA-A*24:02 or HLA-A*02:01 transgenic mice once a week for a total of three times, and a number of peptide-reactive CTLs were identified in the splenocytes. These peptides have better CTL-inducing ability than the peptides of the GPC3 peptide vaccine used in clinical trials. Among these 10 types of common cancer antigens, we will use 5 types of membrane protein common cancer antigens in particular to develop a cocktail mRNA vaccine with the goal of preventing cancer recurrence after surgery. Of course, it is also possible to develop cocktail peptide vaccines. At the same time, we are developing a cocktail CAR/TCR-T cell therapy targeting these common cancer antigens for the treatment of advanced cancer. Citation Format: Tetsuya Nakatsura, Kazumasa Takenouchi, Hiroki Kinoshita, Nobuo Tsukamoto, Kazunobu Ohnuki, Toshihiro Suzuki. Development of a universal cancer vaccine using common cancer antigens cocktail that targets various cancer patients and overcomes the heterogeneity of individual cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5010.