ABSTRACT
In the past few decades, an increasing number of patients are benefiting from treatment with newly developed biologics. Among them, monoclonal antibodies (mAbs), representing a large class of biologics that are highly specific to their targets, have been successful in treating various cancers and autoimmune diseases. However, like other biologics, most protein therapeutics including mAbs elicit a certain level of undesirable ADA responses which may negatively impact product efficacy and/or safety. There have been many achievements of improving tolerability and reducing the immunogenicity of mAbs. Humanized mAbs, which contain replacement of mouse constant regions by human sequences, are less immunogenic than chimeric or murine mAbs. However, humanized and even fully human sequence-derived mAbs may still carry immunological risk. As a requirement of biologics license application (BLA) and Marketing Authorization Application (MAA), the potential impact of the ADA responses on overall clinical efficacy and safety should be characterized and clearly understood as emphasized in Chapter 1. The requirements include validated immunogenicity assays for screening and identifying patients with
positive ADA responses and assessment of the ADA impact on clinical benefit and risk.
