Identification of secretion from cancer cells to suppress T-cell function

2020 Fiscal Year Final Research Report

• Project/Area Number: 19K16799
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 50020:Tumor diagnostics and therapeutics-related
• Research Institution: Osaka University
• Principal Investigator: Hasegawa Kana 大阪大学, 医学系研究科, 特任助教(常勤) (20777370)
• Project Period (FY): 2019-04-01 – 2021-03-31
• Keywords: CAR-T細胞

Outline of Final Research Achievements

CAR-T cell therapy have been already demonstrated efficiency to hematological malignancy as shown by CD19 CAR-T cell to B-cell leukemia/lymphoma. However, their efficacy in solid tumor treatment has not yet been supported. The hurdle which hampers development of solid tumor CAR T cell therapy is lack of appropriate target antigen. We found that R8H283 we previously identified as a novel multiple myeloma-specific monoclonal antibody bound to cancer cells from a part of lung cancer patients. In addition, R8H283-positive cells were not detected in normal tissue of skin and colon by immunohistochemistry, despite the expression of protein itself R8H283 recognized as an antigen. Then, CAR constructs derived from R8H283 were generated and transduced into T cells. The function of R8H283 CAR-T cells was analyzed.

Free Research Field

がん免疫

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が、一方で固形がんに対しては有効なCAR-T細胞療法は未だ存在していない。固形がんに対するCAR-T細胞の開発が進まない最大の原因は、がんに特異性の高い細胞表面抗原の欠如にある。我々は、以前に単離した骨髄腫特異的抗体R8H283が、１）肺がんなどの他のがん種にも結合すること、２）さらには、抗原タンパクを発現している皮膚や大腸などの正常の組織には結合しないことを見出した。これらの結果は、R8H283が固形がんに対するCAR-T細胞研究に役立つ可能性を示唆している。