基于二硫键桥连构建均一性抗体药物偶联物

抗体药物偶联物(ADCs)通过一个化学链接将具高活性药物分子连接到抗体上，协同发挥药物分子的高活性和抗体药物的靶向性的优点，降低毒性，实现靶向精准的疗效。目前已经有10个ADCs陆续上市。在新一代的ADCs发展中定位偶联获得药物–抗体比例(DAR)可控、均一性高的ADCs非常重要。近几年，基于抗体中二硫键先还原再桥连而发展的 “ThioBridge” 技术逐渐显示出其优越性，如用化学方法实现直接对天然抗体的定位修饰、适用性广、DAR值可控、所得 ADCs均一性高等。文章侧重于介绍二硫键桥连构建ADCs的方法和进展。

Disulfide re-bridging for the construction of homogeneous antibody-drug conjugates

Antibody-drug conjugates (ADCs) combine an antibody with highly potent drugs by chemical linkers, allowing to have both the efficacy of payloads and the targeting ability of antibodies for targeted and precise therapeutics. Currently, 10 ADCs have been approved by FDA. It is very important to develop site-specific conjugation method to obtain homogeneous ADCs with controllable drug-antibody ratio (DAR) for the next generation of ADCs. Recently, the “ThioBridge” method that is based on the reduction and re-bridging of the disulfides in an antibody has demonstrated its advantages: a direct chemical method to site-specific modify native antibody, wide applicability, controllable DAR and high homogeneity. Here, we briefly introduce the recent development and progress of disulfide re-bridging methods to construct homogeneous ADCs.