CLIN CANCER RES：工程化分泌检查点抑制剂的CAR-T细胞免疫治疗疗效增强

2017-11-24 MedSci MedSci原创

尽管CAR-T细胞疗法在治疗血液肿瘤方面有一定的治疗效果，但是对实体肿瘤的治疗一直无法达到满意的疗效，其中的部分原因是抑制性肿瘤微环境的作用。CLIN CANCER RES近期发表了一篇文章，作者工程化建立了分泌靶向PD-1检查点抑制剂（CPI）的CAR-T细胞（CAR.αPD1-T）并评估其在人肺癌异种移植模型中的疗效。

尽管CAR-T细胞疗法在治疗血液肿瘤方面有一定的治疗效果，但是对实体肿瘤的治疗一直无法达到满意的疗效，其中的部分原因是抑制性肿瘤微环境的作用。CLIN CANCER RES近期发表了一篇文章，作者工程化建立了分泌靶向PD-1检查点抑制剂（CPI）的CAR-T细胞（CAR.αPD1-T）并评估其在人肺癌异种移植模型中的疗效。

作者在体外实验中评估CAR.αPD1-T细胞功能及扩增能力。抗原特异性刺激后测量IFNγ和细胞增殖情况。使用异种移植模型评估CAR.αPD1-T，CAR-T和CAR-T联合抗PD-1抗体的抗肿瘤效果。通过分析肿瘤浸润淋巴细胞（TIL）浸润和功能分析其机制。研究结果表明，CAR.αPD1-T分泌的人抗PD-1 CPIs可以有效结合PD-1并逆转PD-1/PD-L1介导的T细胞功能抑制作用。持续分泌的抗PD-1导致的PD-1信号阻断可以衰减抑制性T细胞信号，增强T细胞浸润和效应T细胞功能。在异种移植模型中，抗PD-1分泌可以增强CAR-T细胞抗肿瘤活性，延长总生存。

文章最后认为，通过抗PD-1分泌，CAR.αPD1-T功能及扩增能力更强，在清除肿瘤方面的能力优于亲代CAR-T细胞。该研究提供了一种重要的增强CAR-T细胞能力以达到更好的抗肿瘤免疫的方法，特别是在治疗实体肿瘤方面。

原始出处：

Si Li,Natnaree Siriwon,et al.Enhanced Cancer Immunotherapy by Chimeric Antigen Receptor-Modified T Cells Engineered to Secrete Checkpoint Inhibitors.CLIN CANCER RES.November 2017 doi:10.1158/1078-0432.CCR-17-0867

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2017-12-01 gwc392

#分泌#

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2018-03-04 jklm09

#抑制剂#

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2018-05-29 ms3117646317107274

#细胞免疫治疗#

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2018-09-11 仁者大医

#CAR-#

78 0
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2017-11-26 tulenzi

#细胞免疫#

67 0
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