Targeted therapies directed to tumor-associated antigens

Despite advances in cancer therapies in recent years, side effects of systemically administered drugs often remain a dose-limiting factor in therapeutic protocols. To overcome this problem, self-directed localization of therapeutic agents to the disease-affected target tissue has been proposed. For tumor targeting, disease-specific cellular tumor-associated antigens have been exploited for this purpose. This review describes the tumor-associated antigens currently used in the clinic, as well as methods to identify new and more useful ones for future use. Subsequently, ligands that are being used for the recognition of these targets are described, including antibodies and their derivatives, peptides, as well as natural ligands. Furthermore, carrier molecules that will be able to transport the therapeutic moiety to the tumor are discussed, such as liposomes, nanoparticles, viruses, proteins and cells. Finally, various classes of therapeutic moieties that, can be employed in such an approach are listed, including toxins, cytokines, chemical compounds, radionuclides and therapeutic genes. Consideration of the advantages and disadvantages of each component in a tumor-targeted therapeutic agent will allow the rational design of such a construct for maximum clinical efficacy, tailored to the individual needs of the patient.