Ox40 Stimulation And Blockade In Cancer And Inflammatory Disease

The Tumor Necrosis Factor Receptor (TNFR) superfamily consists of 29 membrane and soluble proteins with similar structural features. Many of these molecules are expressed on cells of the immune system and are potential targets for therapeutic intervention in a number of immune based diseases. OX40 (CD134, TNFRSF4) is one TNFR family member that can act as a co-stimulatory receptor for both effector CD4 and CD8 T cells driving proliferation and clonal expansion when ligated by its TNF family ligand, OX40L (CD252, TNFSF4). OX40 signaling can also inhibit the development of suppressive peripheral regulatory T cells (pTreg), as well as promote the activity of innate lymphoid cells such as NK and NKT cells, further amplifying its ability to help an effective immune response. In accordance, many studies in animal models of inflammatory disease, autoimmunity, and transplantation have now shown that blocking OX40/OX40L interactions can reduce the activity of pathogenic T cells and dampen inflammation. Conversely, stimulation of OX40 signaling with agonist antibodies in animals can promote T cell activity that protects against tumor growth as well as T cells that can reduce viral replication. The potential of targeting OX40 or OX40L as a therapy for human immune disease will be discussed, as well as recent and ongoing clinical trials. Disclosure of Interest None declared