Cancer Institute, Xuzhou Medical University, Xuzhou, 221002, Jiangsu, People's Republic of China.
Center of Clinical Oncology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, People's Republic of China.
J Cancer Res Clin Oncol. 2022 Dec;148(12):3511-3520. doi: 10.1007/s00432-022-04248-y. Epub 2022 Aug 12.
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.
前列腺癌可以通过根治性前列腺切除术或根治性放疗获得治愈效果。然而，对于侵袭性更高的高危前列腺癌，最佳治疗方法仍存在争议。嵌合抗原受体 (CAR-T) 表达的工程化 T 淋巴细胞普遍存在浸润能力不足和功能障碍，这是癌症免疫治疗失败的特征。我们进行这项研究是为了探讨多西他赛和 PSMA-CAR-T 细胞联合应用是否能更有效地治疗前列腺癌。
通过流式细胞术检查前列腺癌细胞中前列腺特异性膜抗原 (PSMA) 的表达。通过 ELISA 和 RTCA 评估 PSMA-CAR-T 在体外的疗效。利用人前列腺癌肝转移小鼠模型和人前列腺癌细胞异种移植小鼠模型评估混合治疗的效果。
细胞因子释放和细胞杀伤试验的结果表明，PSMA-CAR-T 细胞在体外对 PSMA 前列腺癌细胞具有特征性的效应功能。此外，PSMA-CAR-T 细胞与多西他赛联合治疗在人前列腺癌小鼠模型中具有协同疗效。这种联合策略可以被视为增强过继性 CAR-T 细胞免疫治疗和减轻化疗不良反应的未开发途径。
PSMA 特异性 CAR-T 细胞与化疗药物多西他赛的合作可以显著改善 NPG 小鼠植入转移性人前列腺癌模型的抗肿瘤效果。
