The evolution of antibodies into versatile tumor-targeting agents.

Abstract

In recent years, monoclonal antibodies have become important weapons in the arsenal of anticancer drugs, and in select cases are now the drugs of choice due to their favorable toxicity profiles. Originally developed to confer passive immunity against tumor-specific antigens, clinical uses of monoclonal antibodies are expanding to include growth factor sequestration, signal transduction modulation, and tumor-specific drug delivery. In this review, we shall present the origins of antibody therapeutics within the field of immunotherapy and their evolution into effective anticancer agents, then discuss their multiple mechanisms of action, the basis of their tumor selectivity, and their therapeutic properties compared with traditional therapies. Antibodies are complex molecules whose efficacy and toxicity depend on the antigen, the antibody, any conjugated groups, and even the patient. Finally, we shall present new technologies being developed to increase the efficacy and selectivity of antibody-based therapeutics. Interestingly, many of the new approaches straddle the middle ground between immunotherapy and the traditional modalities of chemotherapy and radiotherapy, and can be seen as ways of combining the selectivity of the former with the efficacy of the latter.