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大学・研究所にある論文を検索できる 「An oral cancer vaccine using Bifidobacterium vector augments combination of anti-PD-1 and anti-CTLA-4 antibodies in mouse renal cell carcinoma model」の論文概要。リケラボ論文検索は、全国の大学リポジトリにある学位論文・教授論文を一括検索できる論文検索サービスです。

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An oral cancer vaccine using Bifidobacterium vector augments combination of anti-PD-1 and anti-CTLA-4 antibodies in mouse renal cell carcinoma model

Ueki, Hideto Kitagawa, Koichi Kato, Mako Yanase, Shihoko Okamura, Yasuyoshi Bando, Yukari Hara, Takuto Terakawa, Tomoaki Furukawa, Junya Nakano, Yuzo Fujisawa, Masato Shirakawa, Toshiro 神戸大学

2023.06.20

概要

Recently, immune checkpoint inhibitor (ICI) based combination therapies, including anti-PD-1 antibody, nivolumab with anti-CTLA-4 antibody, and ipilimumab have become the primary treatment option for metastatic or unresectable renal cell carcinoma (RCC). However, despite the combination of two ICIs, 60–70% of patients are still resistant to first-line cancer immunotherapy. In the present study, undertook combination immunotherapy for RCC using an oral cancer vaccine (Bifidobacterium longum displaying WT1 tumor associated antigen (B. longum 420)) with anti-PD-1 and anti-CTLA-4 antibodies in a mouse syngeneic model of RCC to explore possible synergistic effects. We found that B. longum 420 significantly improved the survival of mice bearing RCC tumors treated by anti-PD-1 and anti-CTLA-4 antibodies compared to the mice treated by the antibodies alone. This result suggests that B. longum 420 oral cancer vaccine as an adjunct to ICIs could provide a novel treatment option for RCC patients. Our microbiome analysis revealed that the proportion of Lactobacilli was significantly increased by B. longum 420. Although the detailed mechanism of action is unknown, it is possible that microbiome alteration by B. longum 420 enhances the efficacy of the ICIs.

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Author contributions

Research conception and design: H.U., T.S. Data acquisition: H.U., K.K., M.K., S.Y. Statistical analysis: H.U. Data

analysis and interpretation: H.U. Drafting of the manuscript: H.U. Writing of the manuscript: H.U., T.S. Critical

revision of the manuscript: M.F., T.S. Obtaining funding: None. Administrative, technical, or material support:

None. Supervision: T.H., Y.O., Y.B., T.T., J.F., Y.N., M.F. Approval of the final manuscript: M.F., T.S.

Competing interests The authors declare no competing interests.

Additional information

Supplementary Information The online version contains supplementary material available at https://​doi.​org/​

10.​1038/​s41598-​023-​37234-6.

Correspondence and requests for materials should be addressed to T.S.

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