Antitumor activity of EGFR-specific CAR T cells against non-small-cell lung cancer cells in vitro and in mice.

作者: He Li , Yao Huang , Du-Qing Jiang , Lian-Zhen Cui , Zhou He

DOI: 10.1038/S41419-017-0238-6

关键词: In vitroChimeric antigen receptorAntigenCancer researchImmunotherapyReceptorMedicineIn vivoLung cancerCell culture

摘要: Effective control of non-small-cell lung cancer (NSCLC) remains clinically challenging, especially during advanced stages the disease. This study developed an adoptive T-cell treatment through expression a chimeric antigen receptor (CAR) to target human epidermal growth factor (EGFR) in NSCLC. We optimized non-viral piggyBac transposon system engineer T cells for EGFR-CAR, consisting EGFR scFv, transmembrane domain, and intracellular 4-1BB-CD3ζ signaling domains. The modified CAR exhibited expansion capability anticancer efficacy time- antigen-dependent manner vitro as well regression EGFR-positive xenografts vivo. EGFR-CAR therapy is promising strategy improve potency immunotherapy Moreover, could become clinical application NSCLC patients future.

参考文章(41)
Conor E. Steuer, Suresh S. Ramalingam, Targeting EGFR in lung cancer: Lessons learned and future perspectives. Molecular Aspects of Medicine. ,vol. 45, pp. 67- 73 ,(2015) , 10.1016/J.MAM.2015.05.004
Leora Horn, None, Advances in the Treatment of Non-Small Cell Lung Cancer Journal of The National Comprehensive Cancer Network. ,vol. 12, pp. 764- 767 ,(2014) , 10.6004/JNCCN.2014.0185
Hillary G. Caruso, Lenka V. Hurton, Amer Najjar, David Rushworth, Sonny Ang, Simon Olivares, Tiejuan Mi, Kirsten Switzer, Harjeet Singh, Helen Huls, Dean A. Lee, Amy B. Heimberger, Richard E. Champlin, Laurence J.N. Cooper, Tuning Sensitivity of CAR to EGFR Density Limits Recognition of Normal Tissue While Maintaining Potent Antitumor Activity Cancer Research. ,vol. 75, pp. 3505- 3518 ,(2015) , 10.1158/0008-5472.CAN-15-0139
Alla Dolnikov, Sylvie Shen, Guy Klamer, Swapna Joshi, Ning Xu, Lu Yang, Kenneth Micklethwaite, Tracey A. O'Brien, Antileukemic potency of CD19-specific T cells against chemoresistant pediatric acute lymphoblastic leukemia Experimental Hematology. ,vol. 43, pp. 1001- 1014 ,(2015) , 10.1016/J.EXPHEM.2015.08.006
Saumya Ramanayake, Ian Bilmon, David Bishop, Ming-Celine Dubosq, Emily Blyth, Leighton Clancy, David Gottlieb, Kenneth Micklethwaite, Low-cost generation of Good Manufacturing Practice-grade CD19-specific chimeric antigen receptor-expressing T cells using piggyBac gene transfer and patient-derived materials. Cytotherapy. ,vol. 17, pp. 1251- 1267 ,(2015) , 10.1016/J.JCYT.2015.05.013
Xikun Zhou, Jing Li, Zhen Wang, Zhongwen Chen, Ji Qiu, Yinbing Zhang, Wei Wang, Yu Ma, Nongyu Huang, Kaijun Cui, Jiong Li, Yu-quan Wei, Cellular immunotherapy for carcinoma using genetically modified EGFR-specific T lymphocytes. Neoplasia. ,vol. 15, pp. 544- 553 ,(2013) , 10.1593/NEO.13168
James N. Kochenderfer, Mark E. Dudley, Steven A. Feldman, Wyndham H. Wilson, David E. Spaner, Irina Maric, Maryalice Stetler-Stevenson, Giao Q. Phan, Marybeth S. Hughes, Richard M. Sherry, James C. Yang, Udai S. Kammula, Laura Devillier, Robert Carpenter, Debbie-Ann N. Nathan, Richard A. Morgan, Carolyn Laurencot, Steven A. Rosenberg, B-cell depletion and remissions of malignancy along with cytokine-associated toxicity in a clinical trial of anti-CD19 chimeric-antigen-receptor–transduced T cells Blood. ,vol. 119, pp. 2709- 2720 ,(2012) , 10.1182/BLOOD-2011-10-384388
Yozo Nakazawa, Sunandan Saha, Daniel L. Galvan, Leslie Huye, Lisa Rollins, Cliona M. Rooney, Matthew H. Wilson, Evaluation of Long-term Transgene Expression in piggyBac-Modified Human T Lymphocytes Journal of Immunotherapy. ,vol. 36, pp. 3- 10 ,(2013) , 10.1097/CJI.0B013E3182791234
Zhao Chen, Christine M. Fillmore, Peter S. Hammerman, Carla F. Kim, Kwok-Kin Wong, Non-small-cell lung cancers: a heterogeneous set of diseases Nature Reviews Cancer. ,vol. 14, pp. 535- 546 ,(2014) , 10.1038/NRC3775
Steven A. Rosenberg, Nicholas P. Restifo, Adoptive cell transfer as personalized immunotherapy for human cancer. Science. ,vol. 348, pp. 62- 68 ,(2015) , 10.1126/SCIENCE.AAA4967