2022 Fiscal Year Final Research Report
Identification of molecules to induce the constitutive activation of Integrin beta7 in multiple myeloma
| Project/Area Number |
21K15487
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 50010:Tumor biology-related
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| Research Institution | Osaka University |
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Principal Investigator |
Hasegawa Kana 大阪大学, 免疫学フロンティア研究センター, 特任助教(常勤) (20777370)
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| Project Period (FY) |
2021-04-01 – 2023-03-31
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| Keywords | CAR-T細胞 |
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| Outline of Final Research Achievements |
To develop a novel chimeric antigen receptor (CAR)-T cell therapy, a monoclonal antibody (mAb) binding to an antigen specifically expressed in cancer cells is needed. We found that a novel anti-CD98 heavy chain (hc) mAb, R8H283, we previously identified, specifically bound to multiple myeloma (MM) cells due to the difference of N-glycosylation expressed in CD98hc protein between MM cells and normal hematopoietic cells. In addition, R8H283 bound to lung cancer cells but not to normal lung epithelial cells derived from a part of lung cancer patients. CAR-T cells generated from R8H283 demonstrated anti-lung cancer efficacy in mouse model. We had clarified that R8H283 binding was not detected in normal non-hematopoietic tissues expressing CD98hc protein. These results showed that R8H283-derived CAR-T cells were promising as a novel therapy for patients of lung cancer.
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| Free Research Field |
がん免疫
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| Academic Significance and Societal Importance of the Research Achievements |
キメラ抗原受容体－T細胞療法（CAR-T細胞療法）は、血液がんに対して効果を発揮している一方で、固形がんに対してはその開発に未だ成功していない。その理由の一つに、がんに特異性の高い細胞表面抗原の欠如がある。我々は、独自に単離した多発性骨髄腫特異的抗体R8H283の骨髄腫特異性の原因を明らかにした上で、１）R8H283が肺がんに対してもがん特異的結合を示すこと、２）R8H283を元に作製したCAR-T細胞が肺がん細胞に対して抗腫瘍効果を示すことを明らかにした。これらの結果は、R8H283が認識する抗原が肺がんに対するCAR-T細胞療法の新たな治療標的となり得る可能性があることを示唆している。
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