5th World Congress on Cancer Therapy
The General Hospital of PLA, China
Title: The EGFR- targeted chimeric antigen receptor- modified T cells immunotherapy for patients with EGFR- expressing advanced or relapsed/refractory solid tumors
Biography: Weidong Han
In this phase I/II clinical study (NCT01869166), we have evaluated for the fi rst time the safety and effi cacy of EGFR-targeted chimeric antigen receptor-modifi ed T (CAR-T) cells in patients with epidermal growth factor receptor (EGFR) positive (>50% expression), unresectable, and/or relapsed/refractory solid tumors. 24 eligible patients received escalating doses of EGFR-targeted CART cells infusions. Th e EGFR-targeted CART cells were generated from peripheral blood aft er a 10 to 13-day in vitro expansion. Serum cytokines and copy numbers of CAR-EGFR transgene in peripheral blood and in tissue biopsy were monitored periodically. Th e clinical responses were evaluated with RECIST1.1 and immune-related response criteria, and adverse events were graded with CTCAE 4.0. Th e EGFR-targeted CART cells infusions were well-tolerated. Only 3 out of 24 patients exhibited Grade 2 cytokine release syndrome within one week post infusions. Nineteen of 24 evaluable patients (17 lung cancers, 5 cholangiocarcinomas, 1 pancreatic adenocarcinoma, and 1 renal cell carcinoma) had clinical response (DCR=79%), including 2 ongoing CR achieved by patients with cholangiocarcinoma, 4 PR (1 cholangiocarcinoma, 1 pancreatic carcinoma, and 2 lung cancers), and 13SD. Th e median dose of transfused CAR+ T cells was 1.18×107 cells/kg (IQR, 0.76 to 1.43×107 cells/kg). Pathological eradication of EGFR positive tumor cells aft er EGFR-targeted CART cells treatment can be observed in tumor biopsies, along with clear evidence of the CAR-EGFR signal detected in tumor-infi ltrating T cells in all 5 biopsied patients. Th e EGFR-targeted CAR T cells therapy for EGFR-positive, advanced or relapsed/refractory solid tumor patients is safe and eff ective.