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前列腺癌 CAR-T 细胞治疗:当前进展与未来展望

英文原题:CAR-T Cell Therapy for Prostate Cancer: Current Advances and Future Perspectives.

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CAR-T Cell Therapy for Prostate Cancer: Current Advances and Future Perspectives.

PubMed 2025/10/18(内容时间) Biomedicines Q2 · IF 4.5(JCR 2025)

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中文摘要

前列腺癌是全球男性最常确诊的实体器官恶性肿瘤。转移性去势抵抗性前列腺癌是病程进展至终末期、迅速致死的疾病,目前治疗仍以姑息为主,尚无根治手段。嵌合抗原受体(CAR)T细胞疗法的出现彻底改变了难治性血液系统恶性肿瘤的治疗,目前越来越多研究正探索其用于实体瘤的潜力。本综述首先简要介绍前列腺癌当前免疫治疗策略,包括检查点抑制剂、疫苗类方法和双特异性抗体;随后重点讨论该病CAR-T 细胞疗法最新且最有前景的进展。

具体而言,综述考察前列腺癌CAR-T 疗法靶向的关键肿瘤相关抗原,并总结临床前研究及正在进行和已完成的临床试验结果。最后,文章讨论限制CAR-T 治疗前列腺癌疗效的主要挑战,如抗原异质性、免疫抑制性肿瘤微环境、靶向肿瘤同时损伤正常组织的毒性、T细胞持续存在时间有限,以及向转移病灶迁移效率低,并概述克服这些障碍的潜在策略。本文旨在为推动CAR-T 疗法应用于转移性去势抵抗性前列腺癌患者勾勒转化研究路线图。

展开英文摘要原文

Prostate cancer is the most frequently diagnosed solid-organ malignancy in men worldwide. Metastatic castration-resistant prostate cancer represents a rapidly fatal, end-stage form of the disease for which current therapies remain palliative rather than curative.

The advent of chimeric antigen receptor (CAR) T-cell therapy has revolutionized the treatment of refractory hematologic malignancies, and a growing number of studies are now exploring its potential in solid tumors. In this review, we first provide a concise overview of current immunotherapeutic strategies for prostate cancer, including checkpoint inhibitors, vaccine-based approaches, and bispecific antibodies.

We then focus on the most recent and promising developments in CAR-T cell therapy for this malignancy. Specifically, we examine the key tumor-associated antigens targeted in prostate cancer-directed CAR-T cell therapy and summarize findings from preclinical research as well as ongoing and completed clinical trials.

Finally, we discuss the main challenges that limit the efficacy of CAR-T therapy in prostate cancer, such as antigen heterogeneity, immunosuppressive tumor microenvironments, on-target/off-tumor toxicity, limited T-cell persistence, and inefficient trafficking to metastatic lesions, and outline potential strategies to overcome these barriers.

Our aim is to define a translational roadmap for advancing CAR-T therapy toward clinical application in patients with metastatic castration-resistant prostate cancer.

论文信息

作者
Calabrò ML、Ettari R、Di Chio C、De Luca F、Previti S、Zappalà M
单位
Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Viale Stagno d'Alcontres 31, 98166 Messina, Italy.Italy
文献类型
综述
期刊
Biomedicines2025 Oct 18
原文标识
PubMed 41153826 · DOI 10.3390/biomedicines13102545