The next frontier in antibody-drug conjugates: challenges and opportunities in cancer and autoimmune therapy.

Abstract

Antibody-Drug Conjugates (ADCs) have achieved significant success in cancer therapy by combining the targeting specificity of monoclonal antibodies with cytotoxic payloads. However, the concomitant issue of drug resistance has become increasingly prominent, with primary mechanisms including alterations in target antigen expression, impaired drug transport, and inhibition of cell death pathways. ADCs have also shown emerging therapeutic potential in the treatment of autoimmune diseases; for instance, ABBV-3373 has achieved initial success in this area, yet it also faces unique challenges such as the safety of long-term administration, immunogenicity, and heterogeneity of target cells. Addressing these challenges requires multidimensional innovations, including optimizing molecular design, exploring combination therapy strategies, and introducing artificial intelligence (AI)-assisted development. These efforts aim to transition ADCs from the traditional "targeted killing" paradigm to intelligent and personalized precision delivery systems, thereby offering more therapeutic options for patients with cancer and autoimmune diseases.