期刊
ONCOIMMUNOLOGY
卷 6, 期 3, 页码 -出版社
TAYLOR & FRANCIS INC
DOI: 10.1080/2162402X.2017.1284722
关键词
CAR T; MUC1; non-small-cell lung cancer; patient-derived xenograft; PSCA
资金
- National Natural Science Foundation of China (NSFC) [81272329, 81522002, 81570156, 81327801]
- Strategic Priority Research Program of the Chinese Academy of Sciences [XDA01020310]
- Natural Science Fund for Distinguished Young Scholars of Guangdong Province [2014A030306028]
- Guangdong Provincial Applied Science and Technology Research & Development Program [2016B020237006]
- Guangdong Provincial Outstanding Young Scholars Award [2014TQ01R068]
- Guangdong Provincial Basic Research Program [2015B020227003]
- Guangdong Provincial Research and Commercialization Program [2014B090901044]
- Guangdong Province and Chinese Academy of Sciences Joint Program for Research and Commercialization Program [2013B091000010]
- Guangzhou Basic Research Program [201510010186]
- MOST funding of the State Key Laboratory of Respiratory Disease
- National Basic Research Program of China (973 Program) [2011CB504004, 2010CB945500]
- Frontier and key technology innovation special grant from the Department of Science and Technology of Guangdong province [2014B020225005]
- Guangzhou Science Technology and Innovation Commission Project [201504010016]
In recent years, immunotherapies, such as those involving chimeric antigen receptor (CAR) T cells, have become increasingly promising approaches to non-small-cell lung cancer (NSCLC) treatment. In this study, we explored the antitumor potential of prostate stem cell antigen (PSCA)-redirected CAR T and mucin 1 (MUC1)-redirected CAR T cells in tumor models of NSCLC. First, we generated patient-derived xenograft (PDX) mouse models of human NSCLC that maintained the antigenic profiles of primary tumors. Next, we demonstrated the expression of PSCA and MUC1 in NSCLC, followed by the generation and confirmation of the specificity and efficacy of PSCA-and MUC1-targeting CAR T cells against NSCLC cell lines in vitro. Finally, we demonstrated that PSCA-targeting CAR T cells could efficiently suppress NSCLC tumor growth in PDX mice and synergistically eliminate PSCA(+)MUC1(+) tumors when combined with MUC1-targeting CAR T cells. Taken together, our studies demonstrate that PSCA and MUC1 are both promising CAR T cell targets in NSCLC and that the combinatorial targeting of these antigens could further enhance the antitumor efficacy of CAR T cells.
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