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

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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.