Julia Palecki, Amman Bhasin, Andrew Bernstein, Patrick J Mille, William J Tester, Wm Kevin Kelly, Kevin K Zarrabi
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引用次数: 0
摘要
新型 T 细胞免疫疗法,如双特异性 T 细胞吞噬体(BiTEs),正逐渐成为治疗前列腺癌的有效策略。BiTEs 是一种工程化的双特异性抗体,含有两个不同的结合域,可同时与肿瘤相关抗原(TAAs)和免疫效应细胞结合,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,如但不限于 PSMA、PSCA、hK2 和 STEAP1,因此在前列腺癌疾病领域使用 T 细胞重定向 BiTE 具有很强的生物学依据。临床研究中使用的第一代 BiTE 构建物已显示出有意义的抗肿瘤活性,但与给药、免疫原性和治疗相关的不良反应有关的挑战限制了它们的成功。目前,新型生物TE 构建物的开发工作正在继续解决这些障碍,并在疗效和安全性方面取得了可喜的成果。本综述将重点介绍针对晚期前列腺癌患者的生物TE疗法的一些最新进展,以及围绕正在接受临床评估的生物TE构建物不断变化的数据。
T-Cell redirecting bispecific antibodies: a review of a novel class of immuno-oncology for advanced prostate cancer.
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.
期刊介绍:
ACS Applied Energy Materials is an interdisciplinary journal publishing original research covering all aspects of materials, engineering, chemistry, physics and biology relevant to energy conversion and storage. The journal is devoted to reports of new and original experimental and theoretical research of an applied nature that integrate knowledge in the areas of materials, engineering, physics, bioscience, and chemistry into important energy applications.