Abstract:
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.
摘要:
前列腺癌主要是激素依赖性的,和医学治疗集中于通过各种方法抑制雄激素生物合成或信号传导。尽管在引入雄激素受体信号抑制剂(ARSI)方面取得了重大进展,患者继续发展为去势抵抗前列腺癌(CRPC),强调需要超越激素阻断的靶向治疗。嵌合抗原受体(CAR)T细胞和其他工程化免疫细胞代表了新一代过继性细胞疗法。虽然这些疗法显著提高了血液系统恶性肿瘤患者的预后,正在进行的研究正在探索CAR-T疗法在实体肿瘤中的更广泛使用,包括晚期前列腺癌.总的来说,CART细胞疗法对实体癌的疗效较差,免疫抑制性肿瘤微环境阻碍T细胞浸润,抗原识别后的活化和细胞毒性。此外,在晚期前列腺癌患者中存在固有的肿瘤异质性,这可能会阻止使用单靶点药物的持久治疗反应.必须克服这些障碍,以告知临床试验设计并提高治疗效果。在这次审查中,我们讨论了正在研究中的创新和合理设计的策略,以改善前列腺癌细胞免疫治疗的临床翻译,并使这些患者的治疗结果最大化。