Department of Hematology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
Department of Hematology, Affiliated Cancer Hospital of Zhengzhou University and Henan Cancer Hospital, Zhengzhou, Henan, China.
Immunology. 2022 Sep;167(1):15-27. doi: 10.1111/imm.13498. Epub 2022 Jun 11.
Tumour therapy has entered the era of immunotherapy. Monoclonal antibodies (mAb), immune checkpoint inhibitors, chimeric antigen receptor T-cell (CAR-T), cytokine-induced killer (CIK), tumour-infiltrating lymphocytes (TILs) and other cellular immunotherapies have become the focus of current research. The CD47/SIRPα target is becoming another popular tumour immunotherapy target following the PDCD1/CD247(PD1/PD-L1) checkpoint inhibitor. In recent years, a large number of CD47/SIRPα mAbs, fusion proteins, and CD47/SIRPα-based bispecific antibodies (BsAbs) are undergoing preclinical and clinical trials and have good curative effects in the treatment of haematological tumours and solid tumours. They bring new vitality and hope for the treatment of patients with advanced tumours. This review summarizes the research progress of CD47/SIRPα-based BsAbs with different targets for tumour treatment. There are 12 and 9 BsAbs in clinical trials and pre-clinical research, respectively. We report on the mechanism of 15 BsAb molecules with different target and analyse the efficacy and safety of preclinical and clinical trials, discuss the issues that may be faced in the development of CD47-based BsAbs, and dual-target molecules, and summarize their development prospects. This review provides a reference for the safety and effectiveness of BsAbs in clinical application and in the future development of antibodies.
肿瘤治疗已经进入免疫治疗时代。单克隆抗体（mAb）、免疫检查点抑制剂、嵌合抗原受体 T 细胞（CAR-T）、细胞因子诱导的杀伤（CIK）、肿瘤浸润淋巴细胞（TILs）和其他细胞免疫疗法已成为当前研究的焦点。CD47/SIRPα 靶点是继 PDCD1/CD247（PD1/PD-L1）检查点抑制剂之后另一个热门的肿瘤免疫治疗靶点。近年来，大量的 CD47/SIRPα mAbs、融合蛋白和基于 CD47/SIRPα 的双特异性抗体（BsAbs）正在进行临床前和临床试验，并在治疗血液肿瘤和实体瘤方面具有良好的疗效。它们为晚期肿瘤患者的治疗带来了新的活力和希望。本综述总结了基于 CD47/SIRPα 的用于肿瘤治疗的不同靶点的 BsAbs 的研究进展。在临床试验和临床前研究中分别有 12 种和 9 种 BsAbs。我们报告了具有不同靶点的 15 种 BsAb 分子的机制，并分析了临床前和临床试验的疗效和安全性，讨论了在开发基于 CD47 的 BsAbs 和双靶点分子中可能面临的问题，并总结了它们的发展前景。本综述为 BsAbs 在临床应用中的安全性和有效性以及抗体的未来发展提供了参考。
