Monoclonal antibodies in the treatment of malignancy: basic concepts and recent developments

Antibodies have long been considered to be potential anticancer agents because of their specificity for cell-membrane antigens. Applications of hybridoma and recombinant DNA technology have led to the production of unlimited quantities of clinical-grade murine, chimeric, and humanized monoclonal antibodies for clinical use. Whole antibodies may produce anticancer effects in conjunction with the immune system by interaction with complement proteins and/or effector cells via the Fc portion of the antibody molecule. Antibodies may also neutralize circulating ligands or block cell membrane receptors and thus interrupt ligand/receptor interactions and signal transduction that are associated with proliferative or anti-apoptotic effects. The anti-idiotype network cascade provides a rationale for antibodies as vaccine therapy. Antibodies may also serve as the guiding or targeting system for other cytotoxic pharmaceutical products such as (i) radiolabeled antibodies for radioimmunodetection and radioimmunotherapy; (ii) immunotoxins; (iii) chemotherapy/antibody conjugates; (iv) cytokine/antibody conjugates; and (v) immune cell/antibody conjugates. After years of anticipation, as of late 1999 there were four monoclonal antibodies that had been approved by the U.S. Food and Drug Administration based on activity against human malignancy, all of which are in widespread clinical use. Several other products are in various stages of clinical trial testing. Monoclonal antibodies have joined interferon-alpha, interleukin-2 (IL-2), and various hematopoietic growth factors as well-established components of biological therapy, the fourth modality of cancer treatment.