内容紹介
Summary
NKT cells are innate lymphocytes that express an invariant T cell receptor. Since activated NKT cells exert strong anti—tumor responses, NKT cells have been intensively studied for the purpose of their application to cancer immunotherapeutic approaches. Although human peripheral blood contained a very low fraction of NKT cells, and decreased number of NKT cells was also demonstrated in cancer—bearing patients, peripheral blood NKT cells can be activated by ligand—pulsed antigen presenting cells, and can produce a large amount of interferon—γ upon activation. The clinical trials of adoptive transfer of autologous NKT cells were already performed in patients with non—small cell lung cancer, and with head and neck cancer at Chiba University to show its effectiveness and limitation. Meanwhile, RIKEN reported NKT cell regeneration using iPS cell technology in mice, and subsequently established a protocol for regenerating NKT cells from human peripheral blood NKT cells using iPS cell technology. It was confirmed that the iPS cell—derived NKT cells (iPS—NKT) have sufficient expansion capacity and potent direct and indirect cytotoxic activity in the humanized mice models, which suggests their therapeutic competence. We are currently planning an investigator—initiated clinical trial of allogeneic iPS—NKT cell therapy for head and neck cancer.
要旨
NKT細胞は,単一のT細胞抗原受容体を発現する自然免疫系のリンパ球である。特異的糖脂質リガンドによる活性化にて,直接的細胞傷害活性を示すとともに他の免疫細胞を賦活化することによる間接的細胞傷害活性も示すことから,がん治療への応用が期待されている。しかしヒト末梢血中にはNKT細胞分画は非常に低値で,さらに担がん状態では細胞数減少も存在する。これまで千葉大学では,担がん患者末梢血由来NKT細胞をex vivoで増殖させて養子免疫療法を行い,その有効性とともにその限界を示してきた。一方で,理化学研究所においてマウスでのiPS細胞技術を用いたNKT細胞再生が報告され,続いてヒト末梢血NKT細胞からiPS細胞技術を用いてNKT細胞を再生させる方法が確立された。このiPS細胞由来NKT細胞(iPS—NKT)は,ヒト末梢血NKT細胞と同様の直接および間接の細胞傷害活性を有することが確認された。現在,千葉大学医学部附属病院では頭頸部癌に対する他家iPS—NKTを用いた医師主導治験を予定している。
目次
NKT cells are innate lymphocytes that express an invariant T cell receptor. Since activated NKT cells exert strong anti—tumor responses, NKT cells have been intensively studied for the purpose of their application to cancer immunotherapeutic approaches. Although human peripheral blood contained a very low fraction of NKT cells, and decreased number of NKT cells was also demonstrated in cancer—bearing patients, peripheral blood NKT cells can be activated by ligand—pulsed antigen presenting cells, and can produce a large amount of interferon—γ upon activation. The clinical trials of adoptive transfer of autologous NKT cells were already performed in patients with non—small cell lung cancer, and with head and neck cancer at Chiba University to show its effectiveness and limitation. Meanwhile, RIKEN reported NKT cell regeneration using iPS cell technology in mice, and subsequently established a protocol for regenerating NKT cells from human peripheral blood NKT cells using iPS cell technology. It was confirmed that the iPS cell—derived NKT cells (iPS—NKT) have sufficient expansion capacity and potent direct and indirect cytotoxic activity in the humanized mice models, which suggests their therapeutic competence. We are currently planning an investigator—initiated clinical trial of allogeneic iPS—NKT cell therapy for head and neck cancer.
要旨
NKT細胞は,単一のT細胞抗原受容体を発現する自然免疫系のリンパ球である。特異的糖脂質リガンドによる活性化にて,直接的細胞傷害活性を示すとともに他の免疫細胞を賦活化することによる間接的細胞傷害活性も示すことから,がん治療への応用が期待されている。しかしヒト末梢血中にはNKT細胞分画は非常に低値で,さらに担がん状態では細胞数減少も存在する。これまで千葉大学では,担がん患者末梢血由来NKT細胞をex vivoで増殖させて養子免疫療法を行い,その有効性とともにその限界を示してきた。一方で,理化学研究所においてマウスでのiPS細胞技術を用いたNKT細胞再生が報告され,続いてヒト末梢血NKT細胞からiPS細胞技術を用いてNKT細胞を再生させる方法が確立された。このiPS細胞由来NKT細胞(iPS—NKT)は,ヒト末梢血NKT細胞と同様の直接および間接の細胞傷害活性を有することが確認された。現在,千葉大学医学部附属病院では頭頸部癌に対する他家iPS—NKTを用いた医師主導治験を予定している。