An integrated chemical biology platform for discovery of next generation antibody-drug conjugate (ADC) linkers

用于发现下一代抗体药物偶联物 (ADC) 连接体的集成化学生物学平台

• 批准号: 2886428
• 金额: --
• 依托单位: Imperial College London
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2023
• 资助国家: 英国
• 起止时间: 2023 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2886428
• 关键词: integrated; chemical; biology; platform; discovery

Antibody-drug conjugates (ADCs) have decisively impacted cancer treatment, with 10 approvals and >80 progressing though clinical trials. ADCs typically deliver a toxin 'payload' linked to a monoclonal antibody against a protein expressed predominantly on the surface of cancer cells, thereby achieving enhanced on-target activity in tumours. However, despite the great promise of this drug modality, dosing-limiting toxicities often arise from payload release in normal tissue, in some cases leading to product withdrawal.Here you will directly address this unmet need for enhanced specificity of payload release in a collaborative project between the team of Prof Ed Tate at Imperial College and ADC discovery scientists at AstraZeneca. Leveraging a unique discovery platform recently developed in our labs, you will demonstrate proof of concept for an innovative new approach to overcome the challenge of non-specific payload release in ADCs.

抗体药物偶联物（ADC）对癌症治疗产生了决定性的影响，目前已有10项批准，超过80项正在进行临床试验。ADC通常递送与针对主要在癌细胞表面上表达的蛋白质的单克隆抗体连接的毒素“有效载荷”，从而实现肿瘤中增强的靶向活性。然而，尽管这种药物模式有很大的前景，但剂量限制性毒性通常来自正常组织中的有效载荷释放，在某些情况下导致产品撤回。在这里，您将在帝国理工学院的艾德·泰特教授团队和阿斯利康ADC发现科学家之间的合作项目中直接解决这种未满足的增强有效载荷释放特异性的需求。利用我们实验室最近开发的独特发现平台，您将展示一种创新方法的概念验证，以克服ADC中非特异性有效载荷释放的挑战。