基于多价Fc结合多肽构建多特异性抗体的研究

多特异性抗体是最具潜力的抗癌药物之一，但是，受限于制备方法低效、纯化工艺复杂等问题，目前，多特异性抗体的临床应用受到了极大限制。针对这一问题，本项目拟建立一种普适、简便高效的多特异性抗体制备新方法。利用聚谷氨酸（PLG）侧羧基，键合对免疫球蛋白（抗体）恒定区（Fc）具有普遍高亲和力的Fc-III-4C多肽，得到的多价Fc结合多肽PLG-FcIII4C，其可在水溶液中与各种不同单特异性抗体Fc区结合，从而获得多特异性抗体PLG-FcIII4C-Ab-MS。该方法具有如下优点：多特异性抗体通过在水环境中直接孵育制备而成，条件温和，可以最大程度保留原有单克隆抗体的活性；可以高效地构建二、三或四等多特异性抗体，能够丰富多特异性抗体种类，普适性强；制备工艺简单，可降低成本，具有产业化前景。相信未来，依托本项目构建的多特异性抗体可为人类健康事业带来更多希望。

Multi-specific antibodies are one of the most potential anticancer drugs. However, due to problems such as inefficient preparation methods and complex purification processes, the clinical application of multi-specific antibodies is greatly restricted at present. In response to this problem, this project intends to establish a universal, simple and efficient new method for the preparation of multi-specific antibodies. The polyglutamic acid (PLG) side carboxyl group is used to bond the Fc-III-4C polypeptide with generally high affinity to the antibody (IgG) constant region (Fc) to obtain the multivalent Fc-binding polypeptide PLG-FcIII4C, which can be used in aqueous solution combines with the Fc region of various monospecific antibodies to obtain the multi-specific antibody PLG-FcIII4C-Ab-MS. This method has the following advantages: Multi-specific antibodies are prepared by direct incubation in an aqueous environment, and the conditions are mild, and the activity of the original monoclonal antibodies can be retained to the greatest extent. Third and fourth multi-specific antibodies can be constructed efficiently , that can enrich the types of multi-specific antibodies, and have strong universality. The preparation process is simple, the cost can be reduced, and it has industrialization prospects. It is believed that in the future, the multi-specific antibodies built based on this project can bring more hope to human health.