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

  • J Cancer Res Clin Oncol. 2022 Aug 12. doi: 10.1007/s00432-022-04248-y.
Xiaokang Zhang   #  1  2 ,  Shishuo Sun   #  1  2  3 ,  Yangna Miao   #  1  2 ,  Yifan Yuan  1  2 ,  Wanxin Zhao  1  2 ,  Hailong Li  1  4 ,  Xiaohuan Wei  1  2 ,  Chao Huang  1  2 ,  Xiaolei Hu  1  2 ,  Bixi Wang  1  2 ,  Heng Xu  1  2 ,  Wei Zhang  1  2 ,  Xiaoge Gao  1  2  3 ,  Jingyuan Song  1  5 ,  Junnian Zheng  6  7 ,  Qing Zhang  8  9  10
Affiliations
  • 1. Cancer Institute, Xuzhou Medical University, Xuzhou, 221002, Jiangsu, People's Republic of China.
  • 2. Center of Clinical Oncology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, People's Republic of China.
  • 3. Jiangsu Center for the Collaboration and Innovation of Cancer Biotherapy, Xuzhou Medical University, Xuzhou, Jiangsu, People's Republic of China.
  • 4. Department of Urology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, People's Republic of China.
  • 5. School of Nursing, Xuzhou Medical University, Xuzhou, Jiangsu, People's Republic of China.
  • 6. Cancer Institute, Xuzhou Medical University, Xuzhou, 221002, Jiangsu, People's Republic of China. [email protected].
  • 7. Center of Clinical Oncology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, People's Republic of China. [email protected].
  • 8. Cancer Institute, Xuzhou Medical University, Xuzhou, 221002, Jiangsu, People's Republic of China. [email protected].
  • 9. Center of Clinical Oncology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, People's Republic of China. [email protected].
  • 10. Jiangsu Center for the Collaboration and Innovation of Cancer Biotherapy, Xuzhou Medical University, Xuzhou, Jiangsu, People's Republic of China. [email protected].
  • # Contributed equally.
PMID: 35962287 DOI: 10.1007/s00432-022-04248-y
Abstract

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.

Keywords
CAR-T; Combination therapy; Docetaxel; PSMA; Prostate cancer.
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