Journal
CANCERS
Volume 12, Issue 7, Pages -Publisher
MDPI
DOI: 10.3390/cancers12071969
Keywords
NKG2D; CAR T; IL-7; prostate cancer; cell therapy
Categories
Funding
- National Natural Science Foundation of China [81771306, 81072459, 81830083]
- National Key Research and Development Program of China [2016YFC1200400]
- Program for New Century Excellent Talents in University [NCET-12-0179]
- Science and Technology Commission of Shanghai Municipality [201409002900, 14140904200]
- ECNU Public Platform for innovation [011]
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Chimeric antigen receptor (CAR) T-cell therapy is a promising approach in treating solid tumors but the therapeutic effect is limited. Prostate cancer is a typical solid malignancy with invasive property and a highly immunosuppressive microenvironment. Ligands for the NKG2D receptor are primarily expressed on many cancer cells, including prostate cancer. In this study, we utilized NKG2D-based CAR to treat prostate cancer, and improved the therapeutic effect by co-expression of IL-7. The results showed that NKG2D-CAR T cells performed significantly increased cytotoxicity against prostate cancer compared to non-transduced T cells in vitro and in vivo. Moreover, the introduction of theIL-7gene into the NKG2D-CAR backbone enhanced the production of IL-7 in an antigen-dependent manner. NKG2DIL7-CAR T cells exhibited better antitumor efficacy at 16 h and 72 h in vitro, and inhibited tumor growth in xenograft models more effectively. In mechanism, enhanced proliferation and Bcl-2 expression in CD8(+)T cells, decreased apoptosis and exhaustion, and increased less-differentiated cell phenotype may be the reasons for the improved persistence and survival of NKG2DIL7-CAR T cells. In conclusion, these findings demonstrated that NKG2D is a promising option for CAR T-cell therapy on prostate cancer, and IL-7 has enhanced effect on NKG2D-based CAR T-cell immunotherapy, providing a novel adoptive cell therapy for prostate cancer either alone or in combination with IL-7.
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