Monoclonal Antibodies for Immune System-Mediated Diseases

Abstract

Over the last two decades, large molecule biologics such as MONOCLONAL ANTIBODIES (mAbs) have emerged as alternatives to small molecule chemical drugs for treating a wide range of human diseases, including AUTOIMMUNITY and cancer. There are currently over 50 mAbs and 4 Fc-fusion proteins (consisting of an endogenous RECEPTOR molecule linked to the Fc fragment of human IgG) currently approved for human use. Thirty one of these target immunological diseases such as RHEUMATOID ARTHRITIS (RA), MULTIPLE SCLEROSIS (MS), SYSTEMIC LUPUS ERYTHEMATOSUS (SLE), inflammatory bowel disease (IBD), ASTHMA and organ transplant rejection [1]. The success of mAb-based therapeutics is due to their exquisite specificity, which, in combination with their multifunctional properties, high potency, long HALF-LIFE (permitting intermittent dosing and prolonged pharmacological effects) and general lack of off-target toxicity, makes them ideal therapeutics. Over time, knowledge has been acquired to understand what may limit the EFFICACY of mAbs such as immunogenicity and the challenges of certain routes of administration and to have a better understanding of the mechanism of action. This chapter aims to give a general introduction to the immune diseases and inflammatory pathways being targeted by mAbs, focusing on those that are approved or in late-stage clinical development.