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被冷落:超越激素治疗,以 CAR-T 细胞免疫疗法治疗免疫冷前列腺癌

英文原题:Left out in the cold: Moving beyond hormonal therapy for the treatment of immunologically cold prostate cancer with CAR T cell immunotherapies.

查看英文原题

Left out in the cold: Moving beyond hormonal therapy for the treatment of immunologically cold prostate cancer with CAR T cell immunotherapies.

PubMed 2024/06/22(内容时间) J Steroid Biochem Mol Biol Q3 · IF 3.1(JCR 2025)

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中文摘要

前列腺癌主要受激素驱动,现有药物治疗集中于抑制雄激素合成或信号通路。尽管雄激素受体信号抑制剂取得进展,患者仍可能进展为去势抵抗性前列腺癌,因此需要超越激素阻断的靶向疗法。CAR-T 细胞及其他工程化免疫细胞代表新一代过继细胞治疗。此类疗法已改善血液肿瘤结局,针对晚期前列腺癌等实体瘤的研究也在推进,但免疫抑制性肿瘤微环境会阻碍T细胞浸润、活化和杀伤,肿瘤异质性也可能妨碍单靶点治疗产生持久应答。本文综述正在研究的细胞免疫治疗策略,探讨如何克服这些障碍、促进临床转化并改善患者获益。

展开英文摘要原文

Prostate cancer is primarily hormone-dependent, and medical treatments have focused on inhibiting androgen biosynthesis or signaling through various approaches. Despite significant advances with the introduction of androgen receptor signalling inhibitors (ARSIs), patients continue to progress to castration-resistant prostate cancer (CRPC), highlighting the need for targeted therapies that extend beyond hormonal blockade. Chimeric Antigen Receptor (CAR) T cells and other engineered immune cells represent a new generation of adoptive cellular therapies.

While these therapies have significantly enhanced outcomes for patients with hematological malignancies, ongoing research is exploring the broader use of CAR T therapy in solid tumors, including advanced prostate cancer. In general, CAR T cell therapies are less effective against solid cancers with the immunosuppressive tumor microenvironment hindering T cell infiltration, activation and cytotoxicity following antigen recognition.

In addition, inherent tumor heterogeneity exists in patients with advanced prostate cancer that may prevent durable therapeutic responses using single-target agents. These barriers must be overcome to inform clinical trial design and improve treatment efficacy. In this review, we discuss the innovative and rationally designed strategies under investigation to improve the clinical translation of cellular immunotherapy in prostate cancer and maximise therapeutic outcomes for these patients.

论文信息

作者
Porter LH、Harrison SG、Risbridger GP、Lister N、Taylor RA
第一作者单位
Prostate Cancer Research Group, Monash Biomedicine Discovery Institute, Cancer Program, Department of Anatomy and Developmental Biology, Monash University, Clayton, VIC 3800, Australia.Australia
通讯作者单位
Cancer Immunology Program, Cancer Research Division, Peter MacCallum Cancer Centre, Melbourne, VIC 3000, Australia; Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, VIC 3010, Australia; Cabrini Institute, Cabrini Health, Malvern, VIC 3144, Australia; Prostate Cancer Research Group, Monash Biomedicine Discovery Institute, Cancer Program, Department of Physiology, Monash University, Clayton, VIC 3800, Australia. Electronic address: renea.taylor@monash.edu.Australia
文献类型
综述 · 非美国政府资助研究
期刊
The Journal of steroid biochemistry and molecular biology2024 Oct
原文标识
PubMed 38909866 · DOI 10.1016/j.jsbmb.2024.106571