Igawa Tomoyuki
Research Division, Biologics Discovery Department, Chugai Pharmaceutical Co., Ltd.
Yakugaku Zasshi. 2017;137(7):831-836. doi: 10.1248/yakushi.16-00252-3.
Nearly fifty monoclonal antibodies have been approved to date, and the market for monoclonal antibodies is expected to continue to grow. Since global competition in the field of antibody therapeutics is intense, we need to establish novel antibody engineering technologies to provide true benefit for patients, with differentiated product values. Bispecific antibodies are among the next generation of antibody therapeutics that can bind to two different target antigens by the two arms of immunoglobulin G (IgG) molecule, and are thus believed to be applicable to various therapeutic needs. Until recently, large scale manufacturing of human IgG bispecific antibody was impossible. We have established a technology, named asymmetric re-engineering technology (ART)-Ig, to enable large scale manufacturing of bispecific antibodies. Three examples of next generation antibody therapeutics using ART-Ig technology are described. Recent updates on bispecific antibodies against factor IXa and factor X for the treatment of hemophilia A, bispecific antibodies against a tumor specific antigen and T cell surface marker CD3 for cancer immunotherapy, and bispecific antibodies against two different epitopes of soluble antigen with pH-dependent binding property for the elimination of soluble antigen from plasma are also described.
迄今为止，已有近50种单克隆抗体获批，单克隆抗体市场预计将持续增长。由于抗体治疗领域的全球竞争激烈，我们需要建立新型抗体工程技术，以提供具有差异化产品价值的、能真正造福患者的产品。双特异性抗体是下一代抗体治疗药物之一，它可以通过免疫球蛋白G（IgG）分子的两条臂结合两种不同的靶抗原，因此被认为适用于各种治疗需求。直到最近，大规模生产人IgG双特异性抗体还是不可能的。我们已经建立了一种名为不对称再工程技术（ART）-Ig的技术，以实现双特异性抗体的大规模生产。本文描述了使用ART-Ig技术的下一代抗体治疗药物的三个实例。还介绍了用于治疗甲型血友病的抗因子IXa和因子X双特异性抗体、用于癌症免疫治疗的抗肿瘤特异性抗原和T细胞表面标志物CD3双特异性抗体，以及具有pH依赖性结合特性的针对可溶性抗原两个不同表位的双特异性抗体以从血浆中清除可溶性抗原的最新进展。
