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bioRxiv · 10.1101/2024.09.07.611792

PSMA-specific CAR-engineered macrophages for therapy of prostate cancer

Xu, Y.·Xie, D.·Cao, C.·Ju, Y.·Chen, X.·Guan, L.·Li, X.·Zhang, L.·Liang, C.·Yin, X.
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Abstract

Chimeric antigen receptor (CAR)-modified macrophages (CAR-Ms) are a promising approach for the treatment of solid tumors due to its high infiltration and immune-regulation activity. Prostate cancer is a typical solid tumor associated with highly immunosuppressive microenvironment. To date, the potential application of CAR-M cell therapy in prostate cancer has been infrequently explored. The prostate-specific membrane antigen (PSMA) functions as a specific biomarker for prostate cancer. In this study, we assessed the antitumor efficacy of PSMA-targeted CAR-Ms in preclinical models. CAR-Ms were engineered to express a PSMA-specific single-chain variable fragment (scFv) and co-stimulatory domains. In vitro data demonstrated specific cytotoxicity of CAR-Ms against PSMA-expressing prostate cancer cells, which was further supported by transcriptome analysis demonstrating the pro-inflammatory phenotypes of CAR-Ms. In vivo studies using xenograft mouse models confirmed significant tumor regression after administration of PSMA-targeted CAR-Ms compared to controls. Histopathological analysis showed infiltration of CAR-Ms into tumor tissues without off-target toxicity. These results highlight the strong antitumor activity and safety of PSMA-targeted CAR-Ms, supporting their potential as a new immunotherapy for prostate cancer.

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Xu, Y., Xie, D., Cao, C., Ju, Y., Chen, X., Guan, L., Li, X., Zhang, L., Liang, C., Yin, X.. 2024-09-12. PSMA-specific CAR-engineered macrophages for therapy of prostate cancer. https://doi.org/10.1101/2024.09.07.611792

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