TAS0314, a novel multi-epitope long peptide vaccine, showed synergistic antitumor immunity with PD-1/PD-L1 blockade in HLA-A2402 mice

• Published in: Scientific reports Vol. 10; no. 1; p. 17284
• Main Authors: Tanaka, Yuki, Wada, Hiroshi, Goto, Risa, Osada, Toshihiro, Yamamura, Keisuke, Fukaya, Satoshi, Shimizu, Atsushi, Okubo, Mitsuru, Minamiguchi, Kazuhisa, Ikizawa, Koichi, Sasaki, Eiji, Utsugi, Teruhiro
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 14.10.2020; Nature Publishing Group UK
• Subjects: Animals; Antigens; Antitumor activity; B7-H1 Antigen - antagonists & inhibitors; B7-H1 Antigen - genetics; B7-H1 Antigen - immunology; Cancer; Cancer immunotherapy; Cancer vaccines; Cancer Vaccines - administration & dosage; Cancer Vaccines - immunology; Cell Line, Tumor; Clinical trials; Cytotoxicity; Epitopes; Female; Histocompatibility antigen HLA; HLA-A24 Antigen - genetics; HLA-A24 Antigen - immunology; Humans; Immunity; Immunotherapy; Lymphocytes; Lymphocytes T; Mice; Neoplasms - drug therapy; Neoplasms - genetics; Neoplasms - immunology; PD-1 protein; PD-L1 protein; Peptides; Programmed Cell Death 1 Receptor - antagonists & inhibitors; Programmed Cell Death 1 Receptor - genetics; Programmed Cell Death 1 Receptor - immunology; T-Lymphocytes, Cytotoxic - immunology; Tumors; Vaccines; Vaccines, Subunit - administration & dosage
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-020-74187-6

Cancer peptide vaccines are a promising cancer immunotherapy that can induce cancer-specific cytotoxic T lymphocytes (CTLs) in tumors. However, recent clinical trials of cancer vaccines have revealed that the efficacy of the vaccines is limited. Targeting single antigens and vaccination with short peptides are partly the cause of the poor clinical outcomes. We synthesized a novel multi-epitope long peptide, TAS0314, which induced multiple epitope-specific CTLs in HLA knock-in mice. It also showed superior epitope-specific CTL induction and antitumor activity. We also established a combination treatment model of vaccination with PD-1/PD-L1 blockade in HLA-A*2402 knock-in mice, and it showed a synergistic antitumor effect with TAS0314. Thus, our data indicated that TAS0314 treatment, especially in combination with PD-1/PD-L1 blockade, is a promising therapeutic candidate for cancer immunotherapy.