内容紹介
Summary
In the tumor immunotherapy field, the adoptive immunotherapies, in which patient-derived T cells are strengthened ex vivo by activation or genetic modification, have been shown to be effective. However, some issues still remain to be solved. For example, it is not easy to efficiently expand tumor antigen-specific T cells, since they easily get exhausted during ex vivo culture. Moreover, these strategies are costly and time-consuming, because they are mainly conducted in autologous settings. To address these issues, we have been utilizing the induced pluripotent stem(iPS)cell technology. When iPS cells are established from tumor antigen-specific T cells, T cells regenerated from these iPS cells are expected to express the same T cell receptor(TCR)as the original T cells. In line with this concept, we succeeded in regenerating tumor antigen-specific cytotoxic T cells in 2013. We subsequently succeeded in developing a method by which very potent cytotoxic T lymphocytes are regenerated. We are now developing a strategy where non-T derived iPSCs are transduced with exogenous TCR gene efficacy and safety of which have been clinically tested. We plan to apply this approach to HLA haplotype-homozygous iPS cell stock lines, expecting that it will become possible to establish“off-the-shelf T cell”bank against various types of tumors.
要旨
がんの免疫療法の領域では,患者由来のT細胞を体外で遺伝子改変して患者に投与するという養子免疫療法の有効性が示されている。しかし体外でT細胞を培養すると疲弊しやすいという問題がつきまとっていた。さらに養子免疫療法は,主に自家移植の系で行われているためにコストや時間がかかるなどの問題も残されている。これらの障壁を乗り越えるために,筆者らはiPS細胞技術を用いた戦略を進めている。まず,抗原特異的T細胞からiPS細胞を作製し,そのiPS細胞からT細胞を再生すると,すべてが元のT細胞と同じ特異性をもつT細胞になる。このコンセプトに基づいて2013年にメラノーマ抗原MART-1特異的T細胞の再生に成功し,最近さらに高品質なキラーT細胞の分化誘導に成功した。現在,臨床応用に向けて特定のTCR遺伝子をiPS細胞に導入する方法の開発を進めている。この方法をHLAハプロタイプホモiPS細胞株に利用すれば,他家移植用の「即納可能な再生キラーT細胞製剤」を作製できると考えている。
目次
In the tumor immunotherapy field, the adoptive immunotherapies, in which patient-derived T cells are strengthened ex vivo by activation or genetic modification, have been shown to be effective. However, some issues still remain to be solved. For example, it is not easy to efficiently expand tumor antigen-specific T cells, since they easily get exhausted during ex vivo culture. Moreover, these strategies are costly and time-consuming, because they are mainly conducted in autologous settings. To address these issues, we have been utilizing the induced pluripotent stem(iPS)cell technology. When iPS cells are established from tumor antigen-specific T cells, T cells regenerated from these iPS cells are expected to express the same T cell receptor(TCR)as the original T cells. In line with this concept, we succeeded in regenerating tumor antigen-specific cytotoxic T cells in 2013. We subsequently succeeded in developing a method by which very potent cytotoxic T lymphocytes are regenerated. We are now developing a strategy where non-T derived iPSCs are transduced with exogenous TCR gene efficacy and safety of which have been clinically tested. We plan to apply this approach to HLA haplotype-homozygous iPS cell stock lines, expecting that it will become possible to establish“off-the-shelf T cell”bank against various types of tumors.
要旨
がんの免疫療法の領域では,患者由来のT細胞を体外で遺伝子改変して患者に投与するという養子免疫療法の有効性が示されている。しかし体外でT細胞を培養すると疲弊しやすいという問題がつきまとっていた。さらに養子免疫療法は,主に自家移植の系で行われているためにコストや時間がかかるなどの問題も残されている。これらの障壁を乗り越えるために,筆者らはiPS細胞技術を用いた戦略を進めている。まず,抗原特異的T細胞からiPS細胞を作製し,そのiPS細胞からT細胞を再生すると,すべてが元のT細胞と同じ特異性をもつT細胞になる。このコンセプトに基づいて2013年にメラノーマ抗原MART-1特異的T細胞の再生に成功し,最近さらに高品質なキラーT細胞の分化誘導に成功した。現在,臨床応用に向けて特定のTCR遺伝子をiPS細胞に導入する方法の開発を進めている。この方法をHLAハプロタイプホモiPS細胞株に利用すれば,他家移植用の「即納可能な再生キラーT細胞製剤」を作製できると考えている。