Thakur Archana, Lum Lawrence G
a Department of Oncology , Wayne State University and Karmanos Cancer Institute , Detroit , MI , USA.
b Department of Medicine , Wayne State University and Karmanos Cancer Institute , Detroit , MI , USA.
Expert Opin Biol Ther. 2016;16(5):675-88. doi: 10.1517/14712598.2016.1150996. Epub 2016 Mar 16.
Bispecific antibodies (BsAb) are emerging as a novel approach for dual targeting strategies. Two bispecific antibodies are approved for therapy and >30 are in clinical development. The first generation of BsAb were produced by chemical cross-linking or hybridoma technology; with the recent advent of genetic and protein engineering technologies numerous formats of bispecific antibodies have emerged using either the fragments of IgG or whole IgG molecules. Further areas of development include dual blockade of different disease pathways, diagnosis and imaging.
Biologics, including bi- or multi-specific antibodies and T cell-based approaches are rapidly changing the landscape of cancer therapeutics. New engineering platforms for bi- or multi-specific antibodies and scaffolds offer improved efficacy and reduced toxicities over IgG-based monoclonal antibodies. Preclinical and clinical studies using different formats of BsAbs are described in this review using PubMed as a literature search tool.
A comprehensive presentation of preclinical data and clinical trials evaluating the various formats of BsAbs indicate their safety and efficacy. However, a vast opportunity to fine tune physical properties and functional activity of biologics to improve the stability, engagement of cytotoxic CD8 T cells and multi-antigen targeting strategy through protein engineering holds a greater therapeutic potential.
双特异性抗体（BsAb）正作为一种新型的双靶点策略崭露头角。已有两种双特异性抗体获批用于治疗，超过30种正处于临床开发阶段。第一代双特异性抗体是通过化学交联或杂交瘤技术制备的；随着基因和蛋白质工程技术的最新出现，利用IgG片段或完整IgG分子产生了多种形式的双特异性抗体。进一步的发展领域包括对不同疾病途径的双重阻断、诊断和成像。
生物制剂，包括双特异性或多特异性抗体以及基于T细胞的方法正在迅速改变癌症治疗的格局。双特异性或多特异性抗体及支架的新工程平台相较于基于IgG的单克隆抗体具有更高的疗效和更低的毒性。本综述以PubMed作为文献检索工具，描述了使用不同形式双特异性抗体的临床前和临床研究。
对评估各种形式双特异性抗体的临床前数据和临床试验的全面展示表明了它们的安全性和有效性。然而，通过蛋白质工程对生物制剂的物理性质和功能活性进行微调，以提高稳定性、细胞毒性CD8 T细胞的参与度以及多抗原靶向策略，具有更大的治疗潜力。
