A three-company collaboration is redesigning how antibody-drug conjugates—targeted cancer therapies that deliver toxins directly to tumour cells—are manufactured, aiming to cut production costs and improve drug quality. Current ADC manufacturing is complex and expensive. The drugs require chemical linkers to attach the toxin to the antibody, and these linkers often need extra purification steps. The project combines Daresbury Proteins’ modular genetic elements with the National Research Council of Canada’s expression vectors and affinity peptide tags, so the linker is built into the antibody during production. This eliminates the need for separate conjugation and purification steps. If successful, the platform could produce more homogeneous ADC batches—meaning each dose contains a more consistent ratio of drug to antibody—which may improve therapeutic efficacy and reduce side effects. The peptide-based linkers are also less likely to trigger immune responses than current chemical linkers. Crucially, the design allows ADCs to be reconstituted at the bedside, simplifying hospital logistics. Eurofins CDMO Alphora will scale the process for industrial use, potentially lowering costs for a class of drugs that currently costs tens of thousands of pounds per patient.
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The proposed project aims to develop a novel expression platform for high-level production of monoclonal antibodies (mAbs) with optimized affinity peptide tags for development of advanced antibody drug conjugates (ADCs). The project brings together the expertise from Daresbury Proteins Ltd ("Daresbury"), a UK-based company specializing in novel expression platforms, the National Research Council of Canada ("NRC"), a leading national research agency, and Eurofins CDMO Alphora Inc. ("Alphora"), a global Contract Development and Manufacturing Organization (CDMO) for preclinical and clinical development and manufacturing services. The joint initiative will utilize Daresbury's proprietary modular genetic elements for increased transient and stable expression of mAbs, which will be combined with NRC's transient and stable expression vectors and affinity peptide tag linkers for ADC generation. This innovative approach eliminates the need for extra conjugation and purification steps, reducing the complexity and cost of ADC production and ultimately produces ADCs that can be reconstituted in the clinic, thereby simplifying the production processes. The design will be further optimized by Alphora using various analytical and bioprocess engineering strategies to characterize, conjugate, and scale-up the process for a more comprehensive industrial implementation. In addition to enhancing efficiency of ADC production, work outlined in this collaborative project will improve product quality by generating more homogenous ADC batches (thus improving therapeutic efficacy and potentially reducing undesirable side effects), enhancing controlled release mechanism under specific conditions, lowering immunogenicity due to biocompatibility of peptides over small chemical linkers/molecules, and paving path toward bedside formulation and administration of these targeted drugs. By taking advantage of individual strengths of each partner, we aim to overcome some of the major challenges associated with ADC manufacturing and design a more applicable solution for large-scale biopharmaceutical production.
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