2022 Fiscal Year Final Research Report
Characterization of novel acute myeloid leukemia-specific cell surface antigen identified as targets for CAR T cell therapy
| Project/Area Number |
20H03710
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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 | Osaka University |
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Principal Investigator |
Hosen Naoki 大阪大学, 大学院医学系研究科, 教授 (10456923)
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| Project Period (FY) |
2020-04-01 – 2023-03-31
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| Keywords | CAR-T細胞 |
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| Outline of Final Research Achievements |
We identified 32 clones as antibodies that bind to AML cells but do not bind to peripheral blood of healthy individuals other than B cells, using expression cloning methods or LC-MS/MS analysis of immunoprecipitates. The antigens recognized by some candidate antibodies were identified by the random knockout method using CRISPR gRNA libraries. As a result, we identified 22 antigens out of 32 candidate antibodies. Among them, antigen A recognized by antibody X was expressed in normal blood cells and was not leukemia-specific, but antibody binding was leukemia-specific.Therefore, we narrowed down our research targets to them and created CAR-T cells derived from Antibody X, which showed an antitumor effect.
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| Free Research Field |
血液内科学
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| Academic Significance and Societal Importance of the Research Achievements |
がん細胞特異的モノクロ―ナル抗体をできるだけ多く単離し、その後にそれらの抗体が認識する抗原の特性を丹念に解析することにより、網羅的なトランスクリプトーム解析では同的出来ないがん特異的細胞表面抗原を同定できるというコンセプトをAMLにおいても示すことができた。この結果は、新たなAMLに対するCAR-T細胞の臨床開発につながるだけでなく、他のがん種においても同様な試みがなされるべきであることを示唆している。
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