To date, more than 30 antibodies have been approved worldwide for therapeutic use. While the monoclonal antibody market is rapidly growing, the clinical use of therapeutic antibodies is mostly limited to treatment of cancers and immunological disorders. Moreover, antibodies against only five targets (TNF-alpha, HER2, CD20, EGFR, and VEGF) account for more than 80 percent of the worldwide market of therapeutic antibodies. The shortage of novel, clinically proven targets has resulted in the development of many distinct therapeutic antibodies against a small number of proven targets, based on the premise that different antibody molecules against the same target antigen have distinct biological and clinical effects from one another. For example, four antibodies against TNF-alpha have been approved by the FDA -- infliximab, adalimumab, golimumab, and certolizumab pegol -- with many more in clinical and preclinical development. The situation is similar for HER2, CD20, EGFR, and VEGF, each having one or more approved antibodies and many more under development. This review discusses the different binding characteristics, mechanisms of action, and biological and clinical activities of multiple monoclonal antibodies against TNF-alpha, HER-2, CD20, and EGFR and provides insights into the development of therapeutic antibodies.
Animals ; Antibodies, Monoclonal/*pharmacology/therapeutic use ; Antigens, CD20/immunology ; Drug Discovery ; Humans ; Immune System Diseases/*drug therapy/immunology ; *Immunotherapy/trends ; *Molecular Targeted Therapy ; Neoplasms/*drug therapy/immunology ; Receptor, Epidermal Growth Factor/immunology ; Receptor, erbB-2/immunology ; Tumor Necrosis Factor-alpha/immunology ; United States ; United States Food and Drug Administration ; Vascular Endothelial Growth Factor A/immunology

To date, more than 30 antibodies have been approved worldwide for therapeutic use. While the monoclonal antibody market is rapidly growing, the clinical use of therapeutic antibodies is mostly limited to treatment of cancers and immunological disorders. Moreover, antibodies against only five targets (TNF-alpha, HER2, CD20, EGFR, and VEGF) account for more than 80 percent of the worldwide market of therapeutic antibodies. The shortage of novel, clinically proven targets has resulted in the development of many distinct therapeutic antibodies against a small number of proven targets, based on the premise that different antibody molecules against the same target antigen have distinct biological and clinical effects from one another. For example, four antibodies against TNF-alpha have been approved by the FDA -- infliximab, adalimumab, golimumab, and certolizumab pegol -- with many more in clinical and preclinical development. The situation is similar for HER2, CD20, EGFR, and VEGF, each having one or more approved antibodies and many more under development. This review discusses the different binding characteristics, mechanisms of action, and biological and clinical activities of multiple monoclonal antibodies against TNF-alpha, HER-2, CD20, and EGFR and provides insights into the development of therapeutic antibodies.
Animals ; Antibodies, Monoclonal/*pharmacology/therapeutic use ; Antigens, CD20/immunology ; Drug Discovery ; Humans ; Immune System Diseases/*drug therapy/immunology ; *Immunotherapy/trends ; *Molecular Targeted Therapy ; Neoplasms/*drug therapy/immunology ; Receptor, Epidermal Growth Factor/immunology ; Receptor, erbB-2/immunology ; Tumor Necrosis Factor-alpha/immunology ; United States ; United States Food and Drug Administration ; Vascular Endothelial Growth Factor A/immunology

FTY720 is a novel immunomodulator that has proven effective in animal models of transplantation and autoimmunity, has achieved promising results in Phase I and Phase II studies of renal transplantation in humans, and is currently undergoing phase III studies. FTY720 acts as a high-affinity agonist at the sphingosine 1-phosphate receptor-1 (S1P1), where it internalises the receptor and causes alterations to the normal circulation of lymphocytes between the blood and lymphoid tissue. Unlike conventional immunosuppressants, FTY720 does not impair the activation, proliferation or effector functions of T- and B-cells. Further development of FTY720 is in progress, including trials in autoimmune disorders as well as transplantation. This review summarises the mechanism of action of FTY720, its effects in models of transplantation and autoimmunity, and results from clinical trials in humans.
Animals ; Autoimmune Diseases/drug therapy ; Clinical Trials ; Endothelium, Vascular/drug effects ; Humans ; Immune System/drug effects ; Immunosuppressive Agents/*therapeutic use ; *Organ Transplantation ; Propylene Glycols/*therapeutic use ; Receptors, Lysosphingolipid/agonists ; Transplantation Immunology