Resistance to Antibody-Drug Conjugate

Immune therapies have shown significant efficacy in the treatment of pediatric lymphomas. Monoclonal antibodies, whether naked or conjugated have emerged as an attractive option for targeted therapy while minimizing toxicities. Monoclonal antibodies conjugated to small molecule drugs were developed as a way to combine highly potent agents with tumor specificity. Current challenges include careful selection of tumor targets, the management of potential toxicities, identification of ideal patient selection and therapy regimens, and a better understanding of antibody-drug conjugates (ADC) mechanisms of action and resistance. The right combination is critical for a successful ADC. Mechanisms of resistance to ADCs can be inherited to the ADC or acquired by the host environment and can developed against each of the individual components of the ADC. Given the rational design of ADCs, there is the ability to modify each of the components to develop improved agents that can overcome resistance.