2017年3月16日，国际学术期刊《OncoImmunology》在线发表了中国科学院广州生物医药与健康研究院李鹏研究组题为“PSCA and MUC1 in non-small-cell lung cancer as targets of chimeric antigen receptor T cells”的研究成果，研究报道了研究组在体外肺癌细胞系以及肺癌病人来源的异种移植模型中，验证了CAR-PSCA和CAR-MUC1嵌合抗原受体T细胞的有效性和特异性。

 

癌症免疫治疗法曾被science(《科学》)杂志评为2013年十大科学突破，并位居榜首。近年来，嵌合抗原受体T细胞(CAR-T细胞)在B-ALL等白血病的治疗效果特别显著，CAR-CD19已经进入临床试验阶段。因此，CAR-T细胞在实体瘤上的研究应用也紧随其后。

 

李鹏研究组通过在体外对肺癌细胞系进行杀伤实验，验证了研究组构建的分别针对靶点PSCA 和MUC1抗原的CAR-T细胞杀伤的有效性和特异性。进一步，研究组又构建了一些原代的非小细胞肺癌病人(Non-small-cell lung cancer, NSCLC)的异种移植模型(Patient Derived Xenografted model，PDX)，证明了其与人体病理微环境的相似性。研究发现，PDX模型可重建原代肿瘤的细胞形态和表面分子标记物等。

 

研究进一步利用PDX模型，在体内证明了CAR-PSCA和CAR-MUC1嵌合抗原受体t细胞可以有效抑制PDX模型中肿瘤的生长速度，而且CAR-PSCA和CAR-MUC1 T细胞联合使用后，对肿瘤生长的抑制程度更加明显。

 

研究为NSCLC的治疗提供了新CAR-T的治疗靶点，以及联合两种或多种CAR-T细胞的治疗策略，具有重要的临床前应用价值。

 

 

图：NSCLC的PDX模型验证CAR-PSCA和CAR-MUC1 T杀伤作用

 

原文摘要：In recent years, immunotherapies, such as those involving chimeric antigen receptor (CAR) T cells, have become increasingly promising approaches to non-small-cell lung cancer (NSCLC) treatment. In this study, we explored the antitumor potential of prostate stem cell antigen (PSCA)-redirected CAR T and mucin 1 (MUC1)-redirected CAR T cells in tumor models of NSCLC. First, we generated patient-derived xenograft (PDX) mouse models of human NSCLC that maintained the antigenic profiles of primary tumors. Next, we demonstrated the expression of PSCA and MUC1 in NSCLC, followed by the generation and confirmation of the specificity and efficacy of PSCA- and MUC1-targeting CAR T cells against NSCLC cell lines in vitro. Finally, we demonstrated that PSCA-targeting CAR T cells could efficiently suppress NSCLC tumor growth in PDX mice and synergistically eliminate PSCA+MUC1+ tumors when combined with MUC1-targeting CAR T cells. Taken together, our studies demonstrate that PSCA and MUC1 are both promising CAR T cell targets in NSCLC and that the combinatorial targeting of these antigens could further enhance the antitumor efficacy of CAR T cells.