新型四价抗体的优势与基因工程制备方法

近年来基因工程抗体技术发展迅速,将单价小分子抗体改建为双价或多价,成为抗体工程中活跃的领域之一.四价抗体相比于单价或双价抗体在增加抗体亲和力、降低解离率、延长半寿期等药代动力学,受体交联效应等方面具有优势.因此,具有较好的研究和临床应用前景.制备四价抗体的方法主要有化学偶联法和基因工程法,后者主要包括：①通过改变单链抗体VH和VL之间的连接肽的长短对单链抗体之间的聚合作用产生影响;②利用连接肽将scFv进行连接而形成多价抗体分子;③通过寡聚化的结构域,如亮氨酸拉链结构、链亲和素、人p53四聚化功能域、子宫球蛋白等介导多价抗体的形成.

Advantages of Tetravalent Antibody and Its Genetic Engineering Preparation

In recent years, genetic antibody engineering has rapidly developed and become an active field in antibody engineering technologies. It converts small molecule antibodies into bivalent or muhivalent antibodies. Compared with other engineered antibody types, tetravalent antibody displays increased antibody affinity, decreased dissociation rates, prolonged half-life, and enhanced receptor cross-linking effect, which suggests its perspectives in research and clinical applications. Preparation of tetravalent antibodies in the process of antibody engineering includes chemical coupling and genetic engineering methods. The genetic antibody engineering involves： （1） conferring antibody polymerization by changing the length of linker peptide which connects VII and VL of single-chain antibodies; （2） connecting the linker peptide directly to independent scFv to form multiva- lent antibody molecules; （3） mediating formation of multivalent antibodies through oligomerization domains, such as leucine zipper, streptavidin, p53 tetramerization domain, and uteroglobin.