Anti-drug antibodies in the current management of cancer

Monoclonal antibodies (mAbs) have become one of the main therapeutic weapons in modern oncology, mainly as targeted therapies, and immune checkpoint inhibitors. The generation of anti-drug antibodies (ADAs) after their administration can alter their pharmacokinetic, pharmacodynamic, efficacy and safety profile causing infusion-related reactions. Several risk factors have been associated with ADAs development, notably host genetics and immune status, comorbidity, concomitant medications, mAbs molecular structure, dose and route of administration. ADAs are not usually tested on daily clinical practice, being their analysis generally placed in early stages of drug development. ELISA-type assay the most common method. ADAs detection can involve important implications for treatment strategies of cancer patients, guiding therapeutic adjustment. In oncology, some studies about ADAs synthesis related to targeted therapies and immune checkpoint inhibitors have been recently published. Several strategies are proposed to reduce mAbs immunogenicity, such as different schedules, routes of administration or even the use of immunosuppressants. Another question that arises in relation to ADAs generation is the need to measure the concentration levels of active drug to guide the administration schedule. In this review, we will discuss all the aspects that are currently under discussion in relation with ADAs in oncology.