CD137, implications in immunity and potential for therapy

Abstract

CD137 is a member of the TNF receptor family and a potent T cell costimulatory molecule. Crosslinking of CD137 on activated T cells has shown promise in enhancing anti-tumor immune responses in murine models, and agonistic anti-CD137 antibodies are currently being tested in phase I clinical trials. Surprisingly, these very same agonistic anti-CD137 antibodies have also been found to ameliorate autoimmune disease under certain circumstances. At the current state of knowledge these circumstances cannot be clearly defined. Therefore, anti-CD137 antibodies in man will need to be used with caution. CD137 ligand is expressed by antigen presenting cells. Antagonistic anti-CD137 ligand antibodies have shown efficacy in dampening disease in murine autoimmune models. A similar effect would be expected from antagonistic anti-CD137 antibodies, soluble CD137, or any other compound interfering with CD137 / CD137 ligand interaction. CD137 ligand is expressed as a transmembrane protein on the cell surface and it too can transmit signals into antigen presenting cells. Agonistic anti-CD137 ligand antibodies or a recombinant CD137 protein could stimulate the activity of antigen presenting cells.