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 

作者机构：Department of Bio-therapeutic Institute of Basic Medicine Chinese PLA General Hospital Department of Immunology Institute of Basic Medicine Chinese PLA General Hospital Department of Molecular Biology Institute of Basic Medicine Chinese PLA General Hospital 

出 版 物：《Science China(Life Sciences)》 (中国科学（生命科学英文版）)

年 卷 期：2016年第59卷第5期

页      面：468-479页

核心收录：

学科分类：1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学] 

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) 

主　　题：chimeric antigen receptor immunotherapy epidermal growth factor receptor relapsed/refractory non-small cell lungcancer 

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.