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

抗体-药物偶联物（adc）已经对癌症治疗产生了决定性的影响，有10种药物获得批准，80种药物正在进行临床试验。adc通常会传递一种毒素“有效载荷”，这种毒素与一种单克隆抗体相连，这种抗体针对的是一种主要在癌细胞表面表达的蛋白质，从而在肿瘤中实现增强的靶向活性。然而，尽管这种药物模式具有巨大的前景，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停药。在这里，您将直接解决帝国理工学院Ed Tate教授团队和阿斯利康ADC发现科学家之间的合作项目中对增强有效载荷释放特异性的未满足需求。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.