2022 Fiscal Year Final Research Report
Investigating whether antibody production contributes to immune-related adverse events using an acellular protein synthesis system
| Project/Area Number |
20K07676
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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 50020:Tumor diagnostics and therapeutics-related
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| Research Institution | Kobe University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
船越 洋平 神戸大学, 医学部附属病院, 助教 (50566966)
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| Project Period (FY) |
2020-04-01 – 2023-03-31
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| Keywords | 免疫チェックポイント阻害薬 / 免疫関連有害事象 / B細胞 |
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| Outline of Final Research Achievements |
To determine whether antigen-antibody reactions contribute to immune-related adverse events (irAE), B cell kinetics were analyzed in patients receiving a combination therapy of anti-CTLA-4 and anti-PD-1 antibodies. Compared to patients who did not develop irAE, CD21LowB cells, plasmablasts, and plasma cells were significantly increased in 5 patients who experienced grade 3 irAE.
The BCR repertoire was analyzed in a patient who developed irAE hepatitis together with a dramatic increase in the number of activated B cells. BCR gene sequences of CD21LowB cells were ranked according to copy number, and 20 unique sequences with high copy numbers were selected for further analysis. However, single cell analysis did not detect these sequences in CD21LowB cells.
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| Free Research Field |
Medical oncology
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| Academic Significance and Societal Importance of the Research Achievements |
免疫チェックポイント阻害薬の副作用である免疫関連有害事象（irAE）の発症リスクが高い抗CTLA-4抗体と抗PD-1抗体の併用療法を受けた患者のうち、重度のirAEを発症した患者では活性化B細胞サブセットが著増していたのに対し発症しなかった患者では変化がなかったことを示し、特定のirAEでコピー数が増大したBCRレパトアを特定できたことは、シングルセル解析では同じ配列が検出されなかったものの、irAEの発症にB細胞も関与していることを示唆するものであり、irAEの本態解明に資し発症予測や治療法開発につながるもので意義は大きいと考える。
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