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T 细胞重定向双特异性抗体:一种新型免疫肿瘤学药物在晚期前列腺癌中的应用综述。

T-Cell redirecting bispecific antibodies: a review of a novel class of immuno-oncology for advanced prostate cancer.

机构信息

Department of Internal Medicine, Thomas Jefferson University Hospital, Philadelphia, PA, USA.

Department of Medical Oncology, Sidney Kimmel Cancer Center, Thomas Jefferson University Hospital, Philadelphia, PA, USA.

出版信息

Cancer Biol Ther. 2024 Dec 31;25(1):2356820. doi: 10.1080/15384047.2024.2356820. Epub 2024 May 27.

Abstract

Novel T-cell immunotherapies such as bispecific T-cell engagers (BiTEs) are emerging as promising therapeutic strategies for prostate cancer. BiTEs are engineered bispecific antibodies containing two distinct binding domains that allow for concurrent binding to tumor-associated antigens (TAAs) as well as immune effector cells, thus promoting an immune response against cancer cells. Prostate cancer is rich in tumor associated antigens such as, but not limited to, PSMA, PSCA, hK2, and STEAP1 and there is strong biologic rationale for employment of T-cell redirecting BiTEs within the prostate cancer disease space. Early generation BiTE constructs employed in clinical study have demonstrated meaningful antitumor activity, but challenges related to drug delivery, immunogenicity, and treatment-associated adverse effects limited their success. The ongoing development of novel BiTE constructs continues to address these barriers and to yield promising results in terms of efficacy and safety. This review will highlight some of most recent developments of BiTE therapies for patients with advanced prostate cancer and the evolving data surrounding BiTE constructs undergoing clinical evaluation.

摘要

新型 T 细胞免疫疗法,如双特异性 T 细胞衔接器(BiTE),作为治疗前列腺癌的一种很有前途的治疗策略正在兴起。BiTE 是一种工程化的双特异性抗体,包含两个不同的结合域,允许同时与肿瘤相关抗原(TAA)以及免疫效应细胞结合,从而促进针对癌细胞的免疫反应。前列腺癌富含肿瘤相关抗原,如 PSMA、PSCA、hK2 和 STEAP1 等,但不限于这些,并且在前列腺癌疾病领域中使用 T 细胞重定向 BiTE 具有很强的生物学依据。在临床研究中使用的早期一代 BiTE 构建体已经显示出有意义的抗肿瘤活性,但与药物输送、免疫原性和治疗相关的不良反应相关的挑战限制了它们的成功。新型 BiTE 构建体的持续开发继续解决这些障碍,并在疗效和安全性方面取得了有希望的结果。本文将重点介绍一些用于治疗晚期前列腺癌患者的最新 BiTE 治疗方法的进展,以及正在进行临床评估的 BiTE 构建体的不断发展的数据。

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