A mechanistic perspective of monoclonal antibodies in cancer therapy beyond target-related effects.
Several monoclonal antibodies are now in clinical use for cancer therapy, and many others are currently undergoing clinical evaluation. These agents offer unique specificity against key molecular targets on tumor cells or in the tumor microenvironment. The clinical efficacy of monoclonal antibodies is generally attributed to target-specific mechanisms resulting from neutralizing or inhibiting a growth factor or receptor that drives cell proliferation and tumor growth. Several targets, including CD20, human epidermal growth factor receptor 2, vascular endothelial growth factor, and epidermal growth factor receptor, have been validated in specific malignancies on the basis of monoclonal antibody efficacy. However, monoclonal antibodies also have the potential to activate immune-mediated effector functions, including antibody-dependent cell-mediated cytotoxicity and complement-dependent cytotoxicity. These functions result from interactions involving the Fc domain of the antibody, and, consequently, may vary by antibody, isotype, and Fc modification, such as changes in glycosylation. Accordingly, all monoclonal antibodies directed against a given target should not be considered equivalent in their ability to stimulate immune-mediated effector functions.
Strome
Scott E
SE
Department of Otorhinolaryngology, Head and Neck Surgery, University of Maryland School of Medicine, Baltimore, Maryland 21201-1619, USA. sstrome@smail.umaryland.edu
Sausville
Edward A
EA
Mann
Dean
D
D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D000920:Antibody-Dependent Cell Cytotoxicity / Q000276:immunology; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D003165:Complement System Proteins / Q000276:immunology; D003602:Cytotoxicity, Immunologic / Q000276:immunology; D006801:Humans; D007141:Immunoglobulin Fc Fragments / Q000276:immunology; D007132:Immunoglobulin Isotypes / Q000276:immunology; D000922:Immunotoxins / Q000627:therapeutic use; D009369:Neoplasms / Q000188:drug therapy*; D011961:Receptors, Fc / Q000276:immunology
D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D007141:Immunoglobulin Fc Fragments; D007132:Immunoglobulin Isotypes; D000922:Immunotoxins; D011961:Receptors, Fc; D003165:Complement System Proteins