Journal
MOLECULAR THERAPY
Volume 28, Issue 1, Pages 75-88Publisher
CELL PRESS
DOI: 10.1016/j.ymthe.2019.10.010
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Funding
- Beijing Science and Technology Major Project [D171100000517004]
- National Natural Science Foundation of China [31521004, 81874166]
- National Science and Technology Support Project [2014BAI02B01]
- National High Technology Research and Development Program of China [2013ZX10001003003]
- Guangdong Innovative and Entrepreneurial Research Team Program [2014ZT05S216]
- Science and Technology Planning Project of Guangdong Province [2014B020226001]
- Science and Technology Program of Guangzhou [2016B030232001]
- Peking University Clinical Medicine + X Special Project [PKU2017LCX10]
- Ministry of Education of China (111 Project)
- BeiHao Stem Cell and Regenerative Medicine Translational Research Institute
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Chimeric antigen receptor (CAR) T cell therapy remains relatively ineffective against solid tumors due to inadequate infiltration and in vivo expansion of CAR-T cells. Unlike hematological malignancies, solid tumors have vascular barriers that hinder CAR-T cells from reaching the tumor site. Here, we demonstrated that combretastatin A-4 phosphate (CA4P), a vascular disrupting agent (VDA), can significantly improve the infiltration ability of CAR-T cells in solid tumors as evidenced by elevated levels of IFN-gamma. Moreover, combined treatment with CA4P and CAR-T cells greatly increased the therapeutic efficiency of the CAR-T cells in subcutaneous ovarian cancer mouse xenograft models and patient-derived xenograft (PDX) models of colon and ovarian carcinoma. Our findings highlight CA4P as an effective antitumor agent candidate for combination with CAR-T cells in clinical applications to treat solid tumors.
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