2021 Fiscal Year Final Research Report
Developing a personalized immunotherapy: Identification of tumor reactive CTLs
| Project/Area Number |
19K09297
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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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| Review Section |
Basic Section 55040:Respiratory surgery-related
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| Research Institution | Aichi Cancer Center Research Institute (2020-2021)
National Cancer Center Japan (2019) |
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Principal Investigator |
Yoshikawa Toshiaki 愛知県がんセンター(研究所), 腫瘍免疫応答研究分野, 研究員 (00625957)
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| Project Period (FY) |
2019-04-01 – 2022-03-31
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| Keywords | 腫瘍浸潤リンパ球 / 個別化医療 / ネオアンチゲン |
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| Outline of Final Research Achievements |
The antigens encoded by the tumor-specific somatic mutations are potentially best targets for cancer immunotherapy. In this study, to develop a personalized immunotherapy, we characterized the tumor reactive tumor infiltrating lymphocytes (TILs). Surgically resected tumor tissues were obtained from patients with lung cancer. We isolated tumor reactive TILs using proprietary cell surface markers and cloned the T cell receptor (TCR) gene. Patient derived xenografts (PDX) were generated from some primary tumor tissues, and, the reactivity of TILs against autologous PDX cancer cells was evaluated. Furthermore, we performed whole-exome sequencing on matched tumor and normal DNA. We identified the mutated antigens recognized by these TILs. In future, we will try to develop a novel personalized adoptive T cell therapy with enhanced sustained antitumor effect.
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| Free Research Field |
腫瘍免疫学
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| Academic Significance and Societal Importance of the Research Achievements |
肺がんは多くの遺伝子変異を有しており、さらにその多くは患者毎に異なる遺伝子変異であることが報告されている。そのため、これら遺伝子変異由来の抗原を標的とした個別化T細胞療法が実現すれば臨床における治療効果が期待できる。本研究で得られた成果から、TILの中の自己腫瘍反応性TILを効率よく同定、濃縮することが可能となった。今後これらの自己腫瘍反応性TILを若返らせて使用することができれば、根治を目標としたがん治療法として個別化T細胞移入療法を実現できると考えている。
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