Generation of Antibody Drug Conjugate (ADC) technologies for site specific conjugation to toxins

抗体-药物偶联物（adc）是一种靶向治疗技术，用于将毒素直接输送到癌细胞中，是一种快速增长的肿瘤治疗药物，已有8种adc被批准用于临床。大多数临床可用的adc要么是通过赖氨酸e-氨基的化学反应产生异质产物，要么是通过半胱氨酸巯基的偶联反应产生，从而减少链间二硫键，从而降低抗体的稳定性。我们将介绍抗体的位点特异性半胱氨酸突变，用于与有毒药物的位点特异性结合。我们将在功能模型中比较不同的突变抗体作为adc，以确定最佳的稳定性、功能和功效特征。

Antibody-Drug Conjugates (ADCs) are a targeted treatment technology for delivery of toxinsdirectly to cancer cells and a fast-growing class of oncology therapeutics, with eight ADCsapproved for clinical use. Most clinically-available ADCs are produced through either achemical reaction of lysine e-amino groups which produces heterogeneous products, orconjugation through cysteine sulfhydryl groups activated by reducing the interchain disulfidebonds, which may compromise antibody stability. We will introduce site-specific cysteinemutations on antibodies for site-specific conjugation with toxic drugs. We will comparedifferent mutant antibodies as ADCs in functional models, to identify optimal stability,function and efficacy characteristics.