Antibody-Drug Conjugates Face Toxicity Challenges Despite Oncology Advancements
Antibody-drug conjugates (ADCs) have revolutionized oncology by combining monoclonal antibodies with potent small-molecule drugs to target cancer cells. However, a significant challenge limiting their broader application is toxicity, as highlighted by Rongrong Li, senior principal scientist at WuXi AppTec. While the initial concept aimed to deliver therapeutic payloads directly to tumor cells while sparing healthy tissue, preclinical and clinical studies reveal that many adverse effects are driven by payload activity in normal tissues. The toxicity often follows the payload itself, meaning ADCs with the same payload can produce similar adverse effects even when targeting different tumor antigens. For instance, microtubule inhibitors, effective against rapidly dividing tumors, can also harm healthy tissues with continuous cell turnover, leading to toxicities in bone marrow, the gastrointestinal tract, and peripheral nerves. Similarly, DNA-damaging payloads, while designed to impair cancer cells, can cause c...
