
Anti-Idiotype Antibodies, Anti-Drug Antibodies, and Immunogenicity in Biological Therapies: An Integrative Review
Prof. Haluk Ataoglu MD, PhD, CEO
Matriks Biotechnology Co.
Abstract
Biological therapies—including monoclonal antibodies, fusion proteins, and cytokines—are increasingly essential in the management of autoimmune diseases, cancers, and other chronic conditions. However, these agents can elicit immune responses leading to the production of anti-drug antibodies (ADAs). Among these ADAs, anti-idiotype antibodies (anti-Id Abs) specifically target the variable regions (idiotypes) of therapeutic antibodies or other protein biologics. This article provides an overview of the underlying immunological concepts, beginning with Niels Jerne’s network theory, and explores how anti-idiotype antibodies influence the efficacy, safety, and pharmacokinetics of biologics. We discuss the formation, clearance, and pathological potential of immune complexes composed of antibody–anti-idiotype pairs, along with strategies to mitigate unwanted immunogenicity. Special attention is paid to immune checkpoint inhibitors (ICIs) and their immunogenicity profiles. Finally, we offer a summary of current best practices and an outlook on future research directions.
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