| Project/Area Number |
18H02839
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Review Section |
Basic Section 54010:Hematology and medical oncology-related
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| Research Institution | Ehime Prefectural University of Health Science (2020)
Ehime University (2018-2019) |
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Principal Investigator |
YASUKAWA MASAKI 愛媛県立医療技術大学, 保健科学部, 教授 (60127917)
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| Co-Investigator(Kenkyū-buntansha) |
越智 俊元 愛媛大学, 医学系研究科, 講師 (10571086)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥17,550,000 (Direct Cost: ¥13,500,000、Indirect Cost: ¥4,050,000)
Fiscal Year 2020: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2019: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2018: ¥7,280,000 (Direct Cost: ¥5,600,000、Indirect Cost: ¥1,680,000)
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| Keywords | がん免疫療法 / CAR-T細胞 / 一本鎖抗体 / キメラ抗原受容体 (CAR) / 一本鎖抗体ライブラリー / NY-ESO-1 / CD19 / 遺伝子改変T細胞 / 改変抗体 / 二重特異性抗体 / 抗体改変技術 / 遺伝子改変 / キメラ抗原受容体 |
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| Outline of Final Research Achievements |
In this study, we have generated a single-chain antibody generation system in which CAR-library T cells have been screened based on their antitumor functions. A variable region library obtained from the human immunoglobulin was fused with that of an existing antitumor antibody to generate an scFv library. CAR-library T cells which express the scFv library were stimulated with tumor cells to enrich antigen-specific population. As the results, target-specific recognition of newly generated scFv-expressing CAR-T cells could be finely tuned by changing a new variable region. Moreover, scFv-optimized CAR-T cells showed sufficient antitumor cytotoxicity and better proliferation capacity with long-lived T-cell phenotype, resulting in enhanced antitumor effects in humanized mouse in vivo system. Collectively, this system can be applied to generate a new scFv optimal for each CAR-T cell targeting a variety of surface tumor antigens, resulting in further advancement of CAR-T-cell therapy.
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| Academic Significance and Societal Importance of the Research Achievements |
今回我々が確立した新規一本鎖抗体 (scFv)作製技術を用いれば、CAR-T細胞が発現するscFvの標的認識様式を繊細に調律しながら、CAR-T細胞の機能と抗腫瘍効果を最大限に誘導できるscFvを迅速かつ安定して作製することが可能となる。本研究は、これまでと異なる視点から、CAR-T細胞が標的抗原を認識するために重要な働きを担うscFvに着目した。本技術は、これまでに開発されてきた様々な改良型CAR-T細胞の機能をさらに高めることにも応用が可能であることから、難治性がんを標的とした次世代CAR-T細胞療法開発領域におけるインパクトは特に大きく、社会的意義も高いと考えられる。
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