Hushmandi Kiavash, Einollahi Behzad, Lee E Hui Clarissa, Sakaizawa Reo, Glaviano Antonino, Reiter Russel J, Saadat Seyed Hassan, Farani Marzieh Ramezani, Huh Yun Suk, Aref Amir Reza, Salimimoghadam Shokooh, Kumar Alan Prem
Nephrology and Urology Research Center, Clinical Sciences Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran.
Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
Int J Biol Sci. 2025 Jan 27;21(4):1410-1435. doi: 10.7150/ijbs.96155. eCollection 2025.
Conventional immunotherapy has emerged as a key option for cancer treatment. However, its efficacy has been limited in urological cancers, especially prostate cancer, because of the immunosuppressive tumor microenvironment (TME), difficulty in drug delivery, aberrant immune response, and damage to normal cells. Bispecific antibodies (BsAbs) are engineered proteins with two different antigen-binding domains, designed using different technologies and in various formats. BsAb-based tumor immunotherapy has yielded optimistic results in preclinical and clinical investigations of many tumor types, including urological cancers. However, a series of challenges, including tumor heterogeneity, TME, Ab immunogenicity, adverse effects, serum half-life, low response rates, and drug resistance, hamper the application of BsAbs. In this review, we provide insights into the most common BsAb platforms with different mechanisms of action, which are under preclinical and clinical research, along with ways to overcome the challenges in BsAb administration for treating urological cancer.
传统免疫疗法已成为癌症治疗的关键选择。然而，由于免疫抑制性肿瘤微环境（TME）、药物递送困难、异常免疫反应以及对正常细胞的损伤，其在泌尿系统癌症尤其是前列腺癌中的疗效受到限制。双特异性抗体（BsAbs）是具有两个不同抗原结合域的工程蛋白，采用不同技术和多种形式设计而成。基于BsAb的肿瘤免疫疗法在包括泌尿系统癌症在内的多种肿瘤类型的临床前和临床研究中取得了令人乐观的结果。然而，一系列挑战，包括肿瘤异质性、TME、抗体免疫原性、不良反应、血清半衰期、低反应率和耐药性，阻碍了BsAbs的应用。在本综述中，我们深入探讨了具有不同作用机制、正处于临床前和临床研究阶段的最常见BsAb平台，以及克服BsAb给药治疗泌尿系统癌症所面临挑战的方法。
