Chimeric antigen receptor-modified T cells for the immunotherapy of patients with EGFR-expressing advanced relapsed/refractory non-small cell lung cancer  

作　　者：Kaichao Feng Yelei Guo Hanren Dai Yao Wang Xiang Li Hejin Jia Weidong Han 

机构地区：[1]Department of Bio-therapeutic, Institute of Basic Medicine, Chinese PLA General Hospital [2]Department of Immunology, Institute of Basic Medicine, Chinese PLA General Hospital [3]Department of Molecular Biology, Institute of Basic Medicine, Chinese PLA General Hospital

出　　处：《Science China(Life Sciences)》2016年第5期468-479,共12页中国科学（生命科学英文版）

基　　金：supported by the Science and Technology Planning Project of Beijing City (Z151100003915076);the National Natural Science Foundation of China (31270820, 81230061, 81472612, 81402566);the National Basic Science and Development Programme of China (2013BAI01B04);the Nursery Innovation Fund (15KMM50)

摘　　要：The successes achieved by chimeric antigen receptor-modified T （CAR-T） cells in hematological malignancies raised the pos- sibility of their use in non-small lung cancer （NSCLC）. In this phase I clinical study （NCT01869166）, patients with epidermal growth factor receptor （EGFR）-positive （〉50% expression）, relapsed/refractory NSCLC received escalating doses of EGFR-targeted CAR-T cell infusions. The EGFR-targeted CAR-T cells were generated from peripheral blood after a 10 to 13-day in vitro expansion. Serum cytokines in peripheral blood and copy numbers of CAR-EGFR transgene in peripheral blood and in tissue biopsy were monitored periodically. Clinical responses were evaluated with RECISTI.1 and im- mune-related response criteria, and adverse events were graded with CTCAE 4.0. The EGFR-targeted CAR-T cell infusions were well-tolerated without severe toxicity. Of 11 evaluable patients, two patients obtained partial response and five had stable disease for two to eight months. The median dose of transfused CAR＋ T cells was 0.97x 10^7 cells kg J （interquar- tile range （IQR）, 0.45 to 1.09x 10^7 cells kg 1）. Pathological eradication of EGFR positive tumor cells after EGFR-targeted CAR-T cell treatment can be observed in tumor biopsies, along with the CAR-EGFR gene detected in tumor-infiltrating T cells in all four biopsied patients. The EGFR-targeted CAR-T cell therapy is safe and feasible for EGFR-positive advanced re- lapsed/refractory NSCLC.The successes achieved by chimeric antigen receptor-modified T(CAR-T) cells in hematological malignancies raised the possibility of their use in non-small lung cancer(NSCLC). In this phase I clinical study(NCT01869166), patients with epidermal growth factor receptor(EGFR)-positive(>50% expression), relapsed/refractory NSCLC received escalating doses of EGFR-targeted CAR-T cell infusions. The EGFR-targeted CAR-T cells were generated from peripheral blood after a 10 to 13-day in vitro expansion. Serum cytokines in peripheral blood and copy numbers of CAR-EGFR transgene in peripheral blood and in tissue biopsy were monitored periodically. Clinical responses were evaluated with RECIST1.1 and immune-related response criteria, and adverse events were graded with CTCAE 4.0. The EGFR-targeted CAR-T cell infusions were well-tolerated without severe toxicity. Of 11 evaluable patients, two patients obtained partial response and five had stable disease for two to eight months. The median dose of transfused CAR+ T cells was 0.97×10~7 cells kg^(-1)(interquartile range(IQR), 0.45 to 1.09×10~7 cells kg^(-1)). Pathological eradication of EGFR positive tumor cells after EGFR-targeted CAR-T cell treatment can be observed in tumor biopsies, along with the CAR-EGFR gene detected in tumor-infiltrating T cells in all four biopsied patients. The EGFR-targeted CAR-T cell therapy is safe and feasible for EGFR-positive advanced relapsed/refractory NSCLC.

关 键 词：chimeric antigen receptor IMMUNOTHERAPY epidermal growth factor receptor RELAPSED/REFRACTORY non-small cell lungcancer 

分 类 号：R734.2[医药卫生—肿瘤]