title: Chimeric antigen receptor-modified T cells for the immunotherapy of patients with EGFR-expressing advanced relapsed/refractory non-small cell lung cancer.
abstract: 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.
authors.affiliation: Department of Bio-therapeutic, Institute of Basic Medicine, Chinese PLA General Hospital, Beijing, 100853, China.
authors.forename: Kaichao
authors.initials: K
authors.lastname: Feng
authors.affiliation: Department of Immunology, Institute of Basic Medicine, Chinese PLA General Hospital, Beijing, 100853, China.
authors.forename: Yelei
authors.initials: Y
authors.lastname: Guo
authors.affiliation: Department of Immunology, Institute of Basic Medicine, Chinese PLA General Hospital, Beijing, 100853, China.
authors.forename: Hanren
authors.initials: H
authors.lastname: Dai
authors.affiliation: Department of Immunology, Institute of Basic Medicine, Chinese PLA General Hospital, Beijing, 100853, China.
authors.forename: Yao
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Molecular Biology, Institute of Basic Medicine, Chinese PLA General Hospital, Beijing, 100853, China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Bio-therapeutic, Institute of Basic Medicine, Chinese PLA General Hospital, Beijing, 100853, China.
authors.forename: Hejin
authors.initials: H
authors.lastname: Jia
authors.affiliation: Department of Bio-therapeutic, Institute of Basic Medicine, Chinese PLA General Hospital, Beijing, 100853, China. hanwdrsw69@yahoo.com.|Department of Immunology, Institute of Basic Medicine, Chinese PLA General Hospital, Beijing, 100853, China. hanwdrsw69@yahoo.com.|Department of Molecular Biology, Institute of Basic Medicine, Chinese PLA General Hospital, Beijing, 100853, China. hanwdrsw69@yahoo.com.
authors.forename: Weidong
authors.initials: W
authors.lastname: Han
mesh_terms: D000328:Adult; D000368:Aged; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D066246:ErbB Receptors / Q000378:metabolism*; D005260:Female; D006801:Humans; D007167:Immunotherapy; D008175:Lung Neoplasms / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D012008:Recurrence; D013601:T-Lymphocytes / Q000166:cytology*
chemical_list: D011948:Receptors, Antigen, T-Cell; D066246:ErbB Receptors
keywords: chimeric antigen receptor; epidermal growth factor receptor; immunotherapy; non-small cell lung cancer; relapsed/refractory