Chimeric antigen receptor-modified T cells for the immunotherapy of patients with EGFR-expressing advanced relapsed/refractory non-small cell lung cancer
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% expres...
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Published in: | Science China. Life sciences 2016-05, Vol.59 (5), p.468-479 |
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Main Authors: | , , , , , , |
Format: | Article |
Language: | eng |
Subjects: | |
Online Access: | Get full text |
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Summary: | 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. |
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ISSN: | 1674-7305 1869-1889 |