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

• DOI: 10.1007/s00432-022-04248-y
• Publication Date: 2022-08-12T17:03:28Z
• Authors: 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
• Keywords: Male; Receptors, Chimeric Antigen; Myeloid-Derived Suppressor Cells; T-Lymphocytes; Prostate; Prostatic Neoplasms; Docetaxel; Immunotherapy, Adoptive; Xenograft Model Antitumor Assays; 3. Good health; Mice; 03 medical and health sciences; 0302 clinical medicine; Cell Line, Tumor; Humans; Animals; Cytokines

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.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.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.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.