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

抗体-药物结合物(ADC)已经对癌症治疗产生了决定性的影响，已有10项批准，80项正在通过临床试验。ADC通常提供一种毒素‘有效载荷’，与针对主要在癌细胞表面表达的蛋白质的单抗相连，从而在肿瘤中实现更强的靶向活性。然而，尽管这种药物模式前景看好，但剂量限制毒性通常来自正常组织中有效载荷的释放，在某些情况下会导致产品停用。在帝国理工学院的Ed Tate教授和阿斯利康的ADC发现科学家之间的合作项目中，您将直接满足增强有效载荷释放的特异性的这一未满足的需求。利用我们实验室最近开发的独特发现平台，您将展示一种创新的新方法的概念证明，以克服ADC中非特定有效载荷释放的挑战。

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.