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

摘要: The successes achieved by chimeric antigen receptor-modified T (CAR-T) cells in hematological malignancies raised the possibility of their use 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 EGFR-targeted CAR-T cell infusions. were generated from peripheral blood after a 10 to 13-day vitro expansion. Serum cytokines and copy numbers CAR-EGFR transgene tissue biopsy monitored periodically. Clinical responses evaluated RECIST1.1 immune- related response criteria, adverse events graded CTCAE 4.0. infusions well-tolerated without severe toxicity. Of 11 evaluable patients, two obtained partial five had stable disease for eight months. median dose transfused CAR(+) was 0.97×10(7) kg(-1) (interquartile range (IQR), 0.45 1.09×10(7) kg(-1)). Pathological eradication EGFR positive tumor treatment can be observed biopsies, along gene detected tumor-infiltrating all four biopsied patients. therapy is safe feasible EGFR-positive advanced NSCLC.