2019 Fiscal Year Final Research Report
Development of CAR-T therapy targeting amino acid transporter SLC7A1 against colorectal cancer
| Project/Area Number |
16K10476
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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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| Research Field |
General surgery
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| Research Institution | Juntendo University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
小見山 博光 順天堂大学, 医学部, 非常勤講師 (30348982)
神山 博彦 順天堂大学, 医学部, 助教 (00365595)
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| Project Period (FY) |
2016-04-01 – 2020-03-31
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| Keywords | モノクローナル抗体 / トランスポーター / 抗体医薬 / 大腸癌 / 膜分子 / CAT-1 |
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| Outline of Final Research Achievements |
The SLC7A1 is a cationic amino acid transporter with 14 putative transmembrane domains. Among genes in locus 13q12, SLC7A1 gene showed the most significant overexpression specific for colorectal cancer(CRC)-tissues. We assumed that the SLC7A1 involves the growth of CRC cells by our previous study results. Prof. T. Masuko (Kindai Univ.) and his laboratory members produced anti-SLC7A1 monoclonal antibodies. In this study, the basic properties of these monoclonal antibodies were examined. We evaluated the antigen-specific binding activities using a cell line having SLC7A1 hyperexpression. The antibody-dependent cellular cytotoxicity (ADCC) was also evaluated with a CRC cell line as target cells, and human mononuclear cells as effecter cells. Then the high activity was detected by some of these antibodies. It was suggested that,the high potential of the SLC7A1 for atherapeutic target, and that of anti-SLC7A1 antibodies for a drug material in the new molecule target therapy for CRC.
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| Free Research Field |
腫瘍外科学
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| Academic Significance and Societal Importance of the Research Achievements |
大腸癌は抗がん剤治療ではいまだに完治が難しく新規な治療方法の開発が試みられてきた。膜分子は治療標的として適するが、同じ機能性膜タンパクである受容体やチャンネルに比べて、トランスポーターを標的とした医薬開発は進んでいない。抗体取得が難しいとされる多回数膜貫通型であるSLC7A1に対するモノクローナル抗体作成に成功した益子教授らの協力により、SLC7A1をターゲットとした分子標的治療に向けた本研究が可能になった。本研究は大腸癌細胞特異的に高発現するSLC7A1を抗原とする抗体の抗原・大腸癌細胞への結合活性、大腸癌細胞への障害活性などを検証し、新たな大腸癌の分子治療標的医療の有望性を提示した。
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