Long-term eradication of extranodal natural killer/T-cell lymphoma, nasal type, by induced pluripotent stem cell-derived Epstein-Barr virus-specific rejuvenated T cells in vivo
Long-term eradication of extranodal natural killer/T-cell lymphoma, nasal type, by induced pluripotent stem cell-derived Epstein-Barr virus-specific rejuvenated T cells in vivo
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DOI：
10.3324/haematol.2019.223511
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发表时间：
2020-03-01
期刊：
影响因子：
10.1
通讯作者：
Komatsu, Norio
中科院分区：
文献类型：
--
作者：
Ando, Miki;Ando, Jun;Komatsu, Norio
功能再生的诱导多能干细胞（iPSC）衍生的抗原特异性细胞毒性T淋巴细胞（CIL）有望成为一种有效的肿瘤免疫疗法。当含L-门冬酰胺酶的标准化疗在淋巴结自然杀伤/T细胞淋巴瘤鼻型（ENKL）中失败时，不存在有效的挽救治疗。那么临床过程是悲惨的。我们证明了EB病毒特异性iPSC衍生的抗原特异性CTL在体内对ENKL的长期和稳健的根除，iPSC衍生的抗原特异性CTL在小鼠脾脏中作为中央记忆T细胞持续至少六个月。抗肿瘤反应如此强烈，以至于程序性细胞死亡1（PD-1）阻断的任何伴随作用尚不清楚。这些结果表明，长期持续的EB病毒特异性iPSC衍生的抗原特异性CTL有助于持续的抗肿瘤作用，并为复发性和难治性ENKL提供有效的挽救治疗。
Functionally rejuvenated induced pluripotent stem cell (iPSC)-derived antigen-specific cytotoxic T lymphocytes (CIL) are expected to be a potent immunotherapy for tumors. When L-asparaginase-containing standard chemotherapy fails in extranodal natural killer/T-cell lymphoma, nasal type (ENKL), no effective salvage therapy exists. The clinical course then is miserable. We demonstrate prolonged and robust eradication of ENKL in vivo by Epstein-Barr virus-specific iPSC-derived antigen-specific CTL, with iPSC-derived antigen-specific CTL persisting as central memory T cells in the mouse spleen for at least six months. The anti-tumor response is so strong that any concomitant effect of the programmed cell death 1 (PD-1) blockade is unclear. These results suggest that long-term persistent Epstein-Barr virus-specific iPSC-derived antigen-specific CTL contribute to a continuous anti-tumor effect and offer an effective salvage therapy for relapsed and refractory ENKL.