Department of Biotechnology, Higher Education Institute of Rab-Rashid, Tabriz, Iran.
Department of Biology Sciences, Faculty of Sciences, Shahid Rajaee Teacher Training University, Tehran, Iran.
Int J Biol Macromol. 2021 Jan 15;167:1030-1047. doi: 10.1016/j.ijbiomac.2020.11.058. Epub 2020 Nov 14.
Bispecific antibodie (BsAbs) combine two or more epitope-recognizing sequences into a single protein molecule. The first therapeutic applications of BsAbs were focused on cancer therapy. However, these antibodies have grown to cover a wider disease spectrum, including imaging, diagnosis, prophylaxis, and therapy of inflammatory and autoimmune diseases. BsAbs can be categorized into IgG-like formats and non-IgG-like formats. Different technologies have been used for the construction of BsAbs including "CrossMAb", "Quadroma", "knobs-into-holes" and molecular cloning. The mechanism of action for BsAbs includes the induction of CDC, ADCC, ADCP, apoptosis, and recruitment of cell surface receptors, as well as activation or inhibition of signaling pathways. The first clinical trials included mainly leukemia and lymphoma, but solid tumors are now being investigated. The BsAbs bind to a tumor-specific antigen using one epitope, while the second epitope binds to immune cell receptors such as CD3, CD16, CD64, and CD89, with the goal of stimulating the immune response against cancer cells. Currently, over 20 different commercial methods have been developed for the construction of BsAbs. Three BsAbs are currently clinically approved and marketed, and more than 85 clinical trials are in progress. In the present review, we discuss recent trends in the design, engineering, clinical applications, and clinical trials of BsAbs in solid tumors.
双特异性抗体 (BsAbs) 将两个或多个表位识别序列组合成一个单一的蛋白质分子。BsAbs 的第一个治疗应用集中在癌症治疗上。然而，这些抗体已经扩展到涵盖更广泛的疾病谱，包括成像、诊断、预防和炎症性及自身免疫性疾病的治疗。BsAbs 可分为 IgG 样格式和非 IgG 样格式。构建 BsAbs 的不同技术包括“CrossMAb”、“Quadroma”、“knobs-into-holes”和分子克隆。BsAbs 的作用机制包括诱导 CDC、ADCC、ADCP、凋亡和细胞表面受体募集，以及激活或抑制信号通路。第一个临床试验主要包括白血病和淋巴瘤，但现在正在研究实体瘤。BsAbs 用一个表位结合肿瘤特异性抗原，而第二个表位结合免疫细胞受体，如 CD3、CD16、CD64 和 CD89，旨在刺激针对癌细胞的免疫反应。目前，已经开发了超过 20 种不同的商业方法来构建 BsAbs。目前有三种 BsAbs 已在临床上获得批准并上市，还有 85 多项临床试验正在进行中。在本综述中，我们讨论了 BsAbs 在实体瘤中的设计、工程、临床应用和临床试验的最新趋势。
