Co-Expression of IL-7 Improves NKG2D-Based CAR T Cell Therapy on Prostate Cancer by Enhancing the Expansion and Inhibiting the Apoptosis and Exhaustion

Cancers
Cong HeWenzheng Jiang

Abstract

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 the IL-7 gene 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...Continue Reading

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Citations

Dec 10, 2020·Experimental Hematology & Oncology·Hao ZhangHe Huang
Mar 23, 2021·Frontiers in Immunology·Darel Martínez BedoyaDenis Migliorini
Jul 10, 2021·Nature Reviews. Urology·Philipp WolfToni Cathomen
Jul 2, 2021·European Journal of Immunology·Anat Globerson LevinMichel Sadelain
Aug 17, 2021·Frontiers in Immunology·Mercedes Beatriz FuertesNorberto Walter Zwirner

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Methods Mentioned

BETA
transgenic
FACS
Xenograft
flow cytometry
enzyme-linked immunosorbent assay
PCR

Software Mentioned

Prism
GraphPad
FlowJo
image J

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