Docetaxel enhances the therapeutic efficacy of PSMA-specific CAR-T cells against prostate cancer models by suppressing MDSCs.
- Resource Type
- Article
- Authors
- Zhang, Xiaokang; Sun, Shishuo; Miao, Yangna; Yuan, Yifan; Zhao, Wanxin; Li, Hailong; Wei, Xiaohuan; Huang, Chao; Hu, Xiaolei; Wang, Bixi; Xu, Heng; Zhang, Wei; Gao, Xiaoge; Song, Jingyuan; Zheng, Junnian; Zhang, Qing
- Source
- Journal of Cancer Research & Clinical Oncology. Dec2022, Vol. 148 Issue 12, p3511-3520. 10p.
- Subject
- *PROSTATE cancer
*TREATMENT effectiveness
*DOCETAXEL
*MYELOID-derived suppressor cells
*RADICAL prostatectomy
- Language
- ISSN
- 0171-5216
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. 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. 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. [ABSTRACT FROM AUTHOR]