双特异性抗体构建在肿瘤临床治疗中的应用

Bispecific antibodies in clinical tumor therapy

摘要:

双特异性抗体 (Bispecific antibody，BsAb) 是具有两个不同抗原结合位点的抗体，可分为含Fc段和不含Fc段的BsAb，不同结构的BsAb具有不同的特点和应用领域。相比于传统的单克隆抗体，BsAb的灵敏度和特异性更高。更重要的是，BsAb具有募集免疫细胞、双重阻断信号通路等功能，在免疫诊断和治疗中扮演重要角色。随着全球环境的恶化以及人们生活习惯的不规律，肿瘤的发病率越来越高，成为仅次于心脑血管疾病的全球第二大致死疾病，全球每年有1 200万新发癌症病例。肿瘤的治疗手段包括手术切除、放化疗和靶向治疗等。肿瘤免疫疗法是近几年新兴的治疗方法，其通过激发自身免疫系统的能力来清除肿瘤细胞。传统的单抗药物虽在肿瘤靶向治疗和免疫治疗中取得了一定的疗效，但肿瘤具有高度的异质性和可塑性，常常引发肿瘤耐药性的出现。双特异性抗体能够同时靶向多个靶点，目前已用于肿瘤的临床治疗，并取得了一定的治疗效果。文中就双特异性抗体在肿瘤临床治疗中的研究进展和应用作一综述。

Abstract:

Bispeci?c antibody (BsAb) has two different antigen-binding sites, divided into the “IgG-like” format and the “non-IgG-like” format. Different formats have different characteristics and applications. BsAb has higher sensitivity and specificity than conventional antibodies, with special functions such as recruitment of immune cells and blocking of dual signaling pathways, playing an important role in immune-diagnosis and therapy. With the deterioration of the global environment and the irregular living habits of people, the incidence of tumor is becoming higher and higher. Tumor becomes the most serious fatal disease threatening human health after cardiovascular disease. There are 12 million estimated new tumor cases each year worldwide. The major clinical treatments of tumor are surgical resection, chemoradiotherapy, target therapy. Tumor immunotherapy is a novel approach for tumor treatment in recent years, and activates human immune system to control and kill tumor cells. Although the traditional monoclonal antibodies have already acquired some therapeutic effects in tumor targeted therapy and immunotherapy, they induce drug resistance resulted from the heterogeneity and plasticity of tumors. Binding to two target antigens at the same time, BsAb has been used in the clinical treatment of tumors and obtained promising outcomes. This review elaborates the research progress and applications of bispecific antibody in clinical tumor therapy.