@techreport{oai:mie-u.repo.nii.ac.jp:00015268, author = {藤原, 弘 and Fujiwara, Hiroshi}, month = {May}, note = {application/pdf, 難治性骨髄性白血病に対して、新規に白血病ドライバー遺伝子変異由来ネオアンチゲンに特異的なTCR遺伝子導入T細胞(TCR-T)療法開発を続けている。ドライバー遺伝子変異モデルとして成人T細胞性白血病の原因ウイルスHTLV-1由来 p40Tax特異的なTCR-Tを新たに作製して新規細胞免疫療法の有用性を検討した。ネオアンチゲン探索と特異的TCR-T作製法確立を目指して、遺伝子変異を多く持つ大腸がんをモデルに、患者がん細胞の遺伝変異探索と腫瘍浸潤Tリンパ球のTCR遺伝子解析、同ネオアンチゲン特異的TCR-T細胞作製から構成される方法を確立した。以上を基に、AMLを含む他癌種へ解析を広げている。, For the treatment of refractory acute myeloid leukemia (rAML), a currently unmet need, we have been studying the capability of novel adoptive cellular immunotherapy using driver mutation-coded neoantigen reactive T cell receptor (TCR) gene-modified T cells (TCR-T). As a model for driver mutation-coded neoantigen, we chose HTLV-1 p40 Tax, the extrinsic causative factor for adult T-cell leukemia (ATL). We newly achieved HLA-A24 and -A2 restricted TCR αβ genes with high affinities from ATL patients, established TCR gene-modified T cells, and subsequently assessed the capability of this TCR-T therapy. As to development of strategy for neoantigen screening in cancer cells and generation of neoantigen-reactive TCR-T cells using TCR-αβ genes from tumor infiltrating lymphocytes (TIL), instead of rAML, we started to employ cancerous tissues from colon cancer patients, because of its abundance in mutations. Taking above, we are currently expanding this strategy to rAML and other cancers., 2018年度~2020年度科学研究費補助金(基盤研究(C))研究成果報告書, 18K08361}, title = {白血病に対するネオアンチゲン特異的な革新的遺伝子改変ヘルパーT細胞療法の開発}, year = {2021}, yomi = {フジワラ, ヒロシ} }