2022 Fiscal Year Final Research Report
The novel strategy of ubiquitin-fusion cancer vaccine through the specific delivery to XCR1+ Dendritic cells
| Project/Area Number |
20K09086
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 55020:Digestive surgery-related
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| Research Institution | Wakayama Medical University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
山上 裕機 和歌山県立医科大学, 医学部, 学長特命教員(特別顧問) (20191190)
勝田 将裕 和歌山県立医科大学, 医学部, 非常勤講師 (50464673)
尾島 敏康 和歌山県立医科大学, 医学部, 講師 (60448785)
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| Project Period (FY) |
2020-04-01 – 2023-03-31
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| Keywords | Cancer vaccine / Ubiquitin / mesothelin / dendritic cell vaccine |
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| Outline of Final Research Achievements |
We have succeeded in enhancing the anti-tumor effect of XCR1 by conjugating tumor antigens to XCL1, the XCR1 ligand. On the other hand, we have succeeded in enhancing the anti-tumor effect by linking the tumor antigen to the proteolytic signal, ubiquitin. In the present study, based on the results of these two fundamental studies, we aimed to develop a novel method to selectively deliver ubiquitin-fused tumor antigens to XCR1-positive dendritic cells to induce CTLs. First, iPS dendritic cells(iPSDC) were used to stably secure human dendritic cells for the experiments. The iPSDC were gene-transfected with human mesothelin (MSLN) and ubiquitin-MSLN fusion gene. We demonstrated that ubiquitin-MSLN fusion gene-transfected iPSDC induced MSLN-specific CTLs with superior cytotoxicity compared to MSLN alone. XCL1 gene linked to the ubiquitin-fused MSLN, however, had difficulty in work. We reported this study results obtained as iPSDC vaccine therapy using the ubiquitin proteasome system.
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| Free Research Field |
Cancer immunotherapy
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| Academic Significance and Societal Importance of the Research Achievements |
Ub融合がんワクチンを用いたプロテアソーム系での腫瘍抗原の分解亢進および強力なCTL誘導についての結果を報告した。現在、がんに対する治療戦略として免疫チェックポイント阻害療法（ICI）が確立され広く臨床応用されている。しかし、ICI単独治療はがん特異的細胞傷害性リンパ球（CTL）が十分誘導されていないがん患者に対しては効果が乏しい。本研究はこのような患者群に対してがんに対する特異的CTLを効率的に誘導する新たな治療戦略であり、将来的にはICIとの併用によってより癌免疫治療の効果を高める新規治療へとつながる可能性がある。
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