Docetaxel enhances the therapeutic efficacy of PSMA-specific CAR-T cells against prostate cancer models by suppressing MDSCs

多西他赛通过抑制 MDSC 增强 PSMA 特异性 CAR-T 细胞对前列腺癌模型的治疗效果

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作者:Xiaokang Zhang #, Shishuo Sun #, Yangna Miao #, Yifan Yuan, Wanxin Zhao, Hailong Li, Xiaohuan Wei, Chao Huang, Xiaolei Hu, Bixi Wang, Heng Xu, Wei Zhang, Xiaoge Gao, Jingyuan Song, Junnian Zheng, Qing Zhang

Conclusions

Cooperation of PSMA-specific CAR-T cells and the chemotherapy drug docetaxel can impressively ameliorate antitumor effectiveness against an installed metastatic human prostate cancer model in NPG mice.

Methods

Expressions of prostate specific membrane antigen (PSMA) on prostate cancer cells were examined by Flow cytometry. The efficaciousness of PSMA-CAR-T was evaluated in vitro using ELISA and RTCA. The effect of intermixed therapy was assessed in vivo utilizing a human prostate cancer liver metastasis mouse model and a human prostate cancer cell xenograft mouse model.

Purpose

Prostate cancer can undergo curative effects by radical prostatectomy or radical radiotherapy. However, the best treatment for more aggressive high-risk prostate cancer remains controversial. Insufficient infiltration capacity and dysfunction are commonly occurrences in engineered T lymphocytes expressing chimeric antigen receptor (CAR-T), characterizing cancer immunotherapy failure. We conducted this study to investigate whether the combinative application of docetaxel and PSMA-CAR-T cells could be a more effective treatment to prostate cancer.

Results

The outcome of cytokine discharge and cell killing assays demonstrated that PSMA-CAR-T cells have characteristic effector capacity against PSMA+ prostate cancer cells in vitro. Additionally, collaborative treatment of PSMA-CAR-T cells and docetaxel have cooperative efficacy in a mouse model of human prostate cancer. The merged strategy could be seen as an undeveloped avenue to augmenting adoptive CAR-T cell immunotherapy and mitigating the adverse side effects of chemotherapy. Conclusions: Cooperation of PSMA-specific CAR-T cells and the chemotherapy drug docetaxel can impressively ameliorate antitumor effectiveness against an installed metastatic human prostate cancer model in NPG mice.

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