Generation of Antibody Drug Conjugate (ADC) technologies for site specific conjugation to toxins
Generation of Antibody Drug Conjugate (ADC) technologies for site specific conjugation to toxins
批准号:
2395805
负责人:
金额:
$0.0万
依托单位:
依托单位国家:
英国
项目类别:
Studentship
财政年份:
2020
资助国家:
英国
项目状态:
未结题
起止时间:
2020 至 --
中文摘要
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。
英文摘要
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.
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