Journal
SCIENCE CHINA-LIFE SCIENCES
Volume 59, Issue 5, Pages 468-479Publisher
SCIENCE PRESS
DOI: 10.1007/s11427-016-5023-8
Keywords
chimeric antigen receptor; immunotherapy; epidermal growth factor receptor; relapsed/refractory; non-small cell lung cancer
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Funding
- Science and Technology Planning Project of Beijing City [Z151100003915076]
- National Natural Science Foundation of China [31270820, 81230061, 81472612, 81402566]
- National Basic Science and Development Programme of China [2013BAI01B04]
- Nursery Innovation Fund [15KMM50]
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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 CARP T cells was 0.97x10(7) cells kg(-1) (interquartile range (IQR), 0.45 to 1.09x10(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.
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