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Science China Life Sciences

, Volume 59, Issue 5, pp 468–479 | Cite as

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

  • Kaichao Feng
  • Yelei Guo
  • Hanren Dai
  • Yao Wang
  • Xiang Li
  • Hejin Jia
  • Weidong HanEmail author
Open Access
Research Paper

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 0.97×107 cells kg−1 (interquartile range (IQR), 0.45 to 1.09×107 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.

Keywords

chimeric antigen receptor immunotherapy epidermal growth factor receptor relapsed/refractory non-small cell lung cancer 

Supplementary material

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Copyright information

© The Author(s) 2016

Authors and Affiliations

  • Kaichao Feng
    • 1
  • Yelei Guo
    • 2
  • Hanren Dai
    • 2
  • Yao Wang
    • 2
  • Xiang Li
    • 3
  • Hejin Jia
    • 1
  • Weidong Han
    • 1
    • 2
    • 3
    Email author
  1. 1.Department of Bio-therapeutic, Institute of Basic MedicineChinese PLA General HospitalBeijingChina
  2. 2.Department of Immunology, Institute of Basic MedicineChinese PLA General HospitalBeijingChina
  3. 3.Department of Molecular Biology, Institute of Basic MedicineChinese PLA General HospitalBeijingChina

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