An oral cancer vaccine using Bifidobacterium vector augments combination of anti-PD-1 and anti-CTLA-4 antibodies in mouse renal cell carcinoma model
Abstract 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...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2023-06-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-023-37234-6 |
| _version_ | 1797795718945046528 |
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| author | Hideto Ueki Koichi Kitagawa Mako Kato Shihoko Yanase Yasuyoshi Okamura Yukari Bando Takuto Hara Tomoaki Terakawa Junya Furukawa Yuzo Nakano Masato Fujisawa Toshiro Shirakawa |
| author_facet | Hideto Ueki Koichi Kitagawa Mako Kato Shihoko Yanase Yasuyoshi Okamura Yukari Bando Takuto Hara Tomoaki Terakawa Junya Furukawa Yuzo Nakano Masato Fujisawa Toshiro Shirakawa |
| author_sort | Hideto Ueki |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-03-13T03:22:16Z |
| format | Article |
| id | doaj.art-7fe93da284264bc099e20e75187ea979 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-03-13T03:22:16Z |
| publishDate | 2023-06-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-7fe93da284264bc099e20e75187ea9792023-06-25T11:15:33ZengNature PortfolioScientific Reports2045-23222023-06-0113111010.1038/s41598-023-37234-6An oral cancer vaccine using Bifidobacterium vector augments combination of anti-PD-1 and anti-CTLA-4 antibodies in mouse renal cell carcinoma modelHideto Ueki0Koichi Kitagawa1Mako Kato2Shihoko Yanase3Yasuyoshi Okamura4Yukari Bando5Takuto Hara6Tomoaki Terakawa7Junya Furukawa8Yuzo Nakano9Masato Fujisawa10Toshiro Shirakawa11Department of Urology, Kobe University Graduate School of MedicineLaboratory of Translational Research for Biologics, Department of Advanced Medical Science, Kobe University Graduate School of Science, Technology and InnovationLaboratory of Translational Research for Biologics, Department of Advanced Medical Science, Kobe University Graduate School of Science, Technology and InnovationLaboratory of Translational Research for Biologics, Department of Advanced Medical Science, Kobe University Graduate School of Science, Technology and InnovationDepartment of Urology, Kobe University Graduate School of MedicineDepartment of Urology, Kobe University Graduate School of MedicineDepartment of Urology, Kobe University Graduate School of MedicineDepartment of Urology, Kobe University Graduate School of MedicineDepartment of Urology, Kobe University Graduate School of MedicineDepartment of Urology, Kobe University Graduate School of MedicineDepartment of Urology, Kobe University Graduate School of MedicineDepartment of Urology, Kobe University Graduate School of MedicineAbstract 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.https://doi.org/10.1038/s41598-023-37234-6 |
| spellingShingle | Hideto Ueki Koichi Kitagawa Mako Kato Shihoko Yanase Yasuyoshi Okamura Yukari Bando Takuto Hara Tomoaki Terakawa Junya Furukawa Yuzo Nakano Masato Fujisawa Toshiro Shirakawa An oral cancer vaccine using Bifidobacterium vector augments combination of anti-PD-1 and anti-CTLA-4 antibodies in mouse renal cell carcinoma model Scientific Reports |
| title | An oral cancer vaccine using Bifidobacterium vector augments combination of anti-PD-1 and anti-CTLA-4 antibodies in mouse renal cell carcinoma model |
| title_full | An oral cancer vaccine using Bifidobacterium vector augments combination of anti-PD-1 and anti-CTLA-4 antibodies in mouse renal cell carcinoma model |
| title_fullStr | An oral cancer vaccine using Bifidobacterium vector augments combination of anti-PD-1 and anti-CTLA-4 antibodies in mouse renal cell carcinoma model |
| title_full_unstemmed | An oral cancer vaccine using Bifidobacterium vector augments combination of anti-PD-1 and anti-CTLA-4 antibodies in mouse renal cell carcinoma model |
| title_short | An oral cancer vaccine using Bifidobacterium vector augments combination of anti-PD-1 and anti-CTLA-4 antibodies in mouse renal cell carcinoma model |
| title_sort | oral cancer vaccine using bifidobacterium vector augments combination of anti pd 1 and anti ctla 4 antibodies in mouse renal cell carcinoma model |
| url | https://doi.org/10.1038/s41598-023-37234-6 |
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