Antibody–drug conjugates (ADCs) and their journey to autoimmune disease immunotherapy

Antibody–drug conjugates (ADCs) represent a novel and rapidly evolving class of targeted therapeutics that combine the high specificity of monoclonal antibodies (mAbs) with the potent cytotoxic effects of small-molecule drugs. These engineered molecules are designed to selectively deliver cytotoxic agents to specific cells, thereby reducing off-target toxicity and enhancing therapeutic efficacy. In oncology, ADCs have already demonstrated significant clinical success, particularly in the treatment of hematological malignancies and solid tumors. Agents such as trastuzumab emtansine and brentuximab vedotin exemplify how ADCs can effectively target cancer cells while limiting damage to healthy tissues. Over the past decade, the development of new linkers, payloads, and antibody engineering technologies has further refined the safety and effectiveness of ADCs, leading to an expanded pipeline of approved and investigational compounds. Following their success in oncology, interest has grown in repurposing ADCs for the treatment of non-malignant diseases, including autoimmune disorders. These conditions are characterised by inappropriate immune responses in which autoreactive cells and inflammatory mediators attack host tissues. ADCs offer a promising solution by enabling the selective depletion or modulation of these pathogenic immune cell subsets without broadly suppressing the entire immune system. Preclinical and early clinical studies have shown encouraging results. For instance, ADCs targeting CD19 or CD22 are being explored for systemic lupus erythematosus and other B-cell-driven diseases, while anti-CD3 ADCs have shown potential in type 1 diabetes. As knowledge of disease-specific immune targets increases, ADCs may provide a new avenue for achieving durable remission in autoimmune diseases with improved safety profiles compared to conventional immunosuppressants. This presentation comprehensively explores the evolving landscape of ADCs in autoimmune therapeutics.