Antibody-Drug Conjugates (ADCs)

Abstract

The concept of ADCs emerged from the convergence of advancements in monoclonal antibody technology and drug delivery systems in the late 20th century. Early attempts to conjugate antibodies with cytotoxic drugs faced challenges related to stability, linker chemistry, and immunogenicity. At the heart of an ADC is the monoclonal antibody, which serves as the targeting moiety. These antibodies are designed to recognize and bind to specific antigens overexpressed on the surface of cancer cells, such as tumor-associated antigens (TAAs) or cell surface receptors. The choice of antibody is critical, as it determines the specificity and affinity for the target antigen, influencing both the therapeutic efficacy and safety profile of the ADC. The linkage between the antibody and the payload, known as the linker, plays a crucial role in stabilizing the conjugate in circulation, facilitating selective release of the payload within the tumor microenvironment, and minimizing premature drug release in healthy tissues.