Yang Fa, Wen Weihong, Qin Weijun
Department of Urology, Xijing Hospital, Fourth Military Medical University, 127 Changle West Road, Xi'an 710032, China.
Department of Immunology, Fourth Military Medical University, 169 Changle West Road, Xi'an 710032, China.
Int J Mol Sci. 2016 Dec 28;18(1):48. doi: 10.3390/ijms18010048.
With the development of molecular cloning technology and the deep understanding of antibody engineering, there are diverse bispecific antibody formats from which to choose to pursue the optimal biological activity and clinical purpose. The single-chain-based bispecific antibodies usually bridge tumor cells with immune cells and form an immunological synapse because of their relatively small size. Bispecific antibodies in the IgG format include asymmetric bispecific antibodies and homodimerized bispecific antibodies, all of which have an extended blood half-life and their own crystalline fragment (Fc)-mediated functions. Besides retargeting effector cells to the site of cancer, new applications were established for bispecific antibodies. Bispecific antibodies that can simultaneously bind to cell surface antigens and payloads are a very ideal delivery system for therapeutic use. Bispecific antibodies that can inhibit two correlated signaling molecules at the same time can be developed to overcome inherent or acquired resistance and to be more efficient angiogenesis inhibitors. Bispecific antibodies can also be used to treat hemophilia A by mimicking the function of factor VIII. Bispecific antibodies also have broad application prospects in bone disorders and infections and diseases of the central nervous system. The latest developments of the formats and application of bispecific antibodies will be reviewed. Furthermore, the challenges and perspectives are summarized in this review.
随着分子克隆技术的发展以及对抗体工程的深入理解，有多种双特异性抗体形式可供选择，以追求最佳的生物学活性和临床目的。基于单链的双特异性抗体通常由于其相对较小的尺寸而将肿瘤细胞与免疫细胞连接起来并形成免疫突触。IgG形式的双特异性抗体包括不对称双特异性抗体和同二聚化双特异性抗体，它们都具有延长的血液半衰期以及自身的结晶片段（Fc）介导的功能。除了将效应细胞重新靶向癌症部位外，双特异性抗体还建立了新的应用。能够同时结合细胞表面抗原和有效载荷的双特异性抗体是一种非常理想的治疗用途递送系统。可以开发能够同时抑制两个相关信号分子的双特异性抗体，以克服内在或获得性耐药性，并成为更有效的血管生成抑制剂。双特异性抗体还可通过模拟因子VIII的功能用于治疗甲型血友病。双特异性抗体在骨骼疾病、感染和中枢神经系统疾病中也具有广阔的应用前景。本文将综述双特异性抗体形式和应用的最新进展。此外，本综述还总结了挑战和前景。
