National Clinical Research Center for Normal Aging and Geriatric & Department of Oncology & Institute of Geriatric & The Key Lab of Normal Aging and Geriatric, The Second Medical Centre, PLA General Hospital, Beijing, China.
Medical of School & Graduate School, Nankai University, Tianjin, China.
J Immunol Res. 2019 Feb 11;2019:4516041. doi: 10.1155/2019/4516041. eCollection 2019.
Bispecific antibodies (BsAbs) are a sort of dual functional proteins with specific binding to two distinct targets, which have become a focus of interest in antibody engineering and drug development research and have a promising future for wide applications in cancer immunotherapy and autoimmune disease. The key of clinical application and commercial-scale manufacturing of BsAbs is the amenability to assembly and purification of desired heterodimers. Advances in genetic engineering technology had resulted in the development of diverse BsAbs. Multiple recombinant strategies have been used to solve the mispairing problem between light and heavy chains, as well as to enforce accurate dimerization of heterologous heavy chains. There are 23 platforms available to generate 62 BsAbs which can be further divided into IgG-like ones and fragment-based ones, and more than 50 molecules are undergoing clinical trials currently. BsAbs with IgG-like architecture exhibit superior advantages in structure (similar to natural antibodies), pharmacokinetics, half-life, FcR-mediated function, and biological activity. This review considers various IgG-like BsAb generation approaches, summarizes the clinical applications of promising new BsAbs, and describes the mechanism of BsAbs in tumor therapy.
双特异性抗体(BsAbs)是一类具有特异性结合两个不同靶标的双功能蛋白,已成为抗体工程和药物开发研究的热点,在癌症免疫治疗和自身免疫性疾病中有广泛应用的前景。BsAbs 临床应用和商业化生产的关键是具有期望异源二聚体组装和纯化的能力。基因工程技术的进步已经产生了多种 BsAbs。已经使用多种重组策略来解决轻链和重链之间的错配问题,并强制异源重链的准确二聚化。有 23 个平台可用于生成 62 种 BsAbs,它们可以进一步分为 IgG 样和基于片段的 BsAbs,目前有超过 50 种分子正在进行临床试验。具有 IgG 样结构的 BsAbs 在结构(类似于天然抗体)、药代动力学、半衰期、FcR 介导的功能和生物活性方面具有优势。本文综述了各种 IgG 样 BsAb 的生成方法,总结了有前途的新型 BsAbs 的临床应用,并描述了 BsAbs 在肿瘤治疗中的作用机制。
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