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

生成用于与毒素进行位点特异性缀合的抗体药物缀合物 (ADC) 技术

• 批准号: 2395805
• 金额: --
• 依托单位: King's College London
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2020
• 资助国家: 英国
• 起止时间: 2020 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2395805
• 关键词: Generation; Antibody; Drug; Conjugate; ADC

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.

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。