Use of an Antibody to Target Geldanamycin

Extract

The promise of antibodies as mediators of effective targeted anticancer therapy is beginning to be fulfilled. In the past few years, two monoclonal antibodies (MAbs) have been approved for selective use by the U.S. Food and Drug Administration (FDA) (Rockville, MD) and incorporated into standard therapy, resulting in improved clinical responses and prolongation of life. The most dramatic clinical response has been to rituximab, which is directed against the CD-20 antigen on lymphoma cells (1). Herceptin against the HER2 receptor has proved to be effective in combination with chemotherapy for a subpopulation of breast cancer patients whose malignant cells express high levels of this receptor (2).

Since the discovery of methods for producing large quantities of MAbs by Kohler and Milstein in 1975 (3), investigators have explored the following three ways of using MAbs to treat cancer: 1) as mediators of immune cytotoxicity through activation of complement or by action of lymphocytes and macrophages, 2) as inhibitors of specific functions mediated by the targeted antigen, and 3) as carriers of cytotoxic molecules or radionuclides to cells bearing the relevant antigen. The article by Mandler et al. (4) in this issue of the Journal combines the second and third approaches.