Tumor necrosis factor receptor superfamily member 4 (OX40) (OX40)

Tumor necrosis factor receptor superfamily member 4 (OX40), also known as CD134, is a critical costimulatory receptor primarily expressed on the surface of activated CD4+ and CD8+ T cells (UniProt: P43489). Its interaction with the OX40 ligand (OX40L) promotes T cell survival, proliferation, and the production of cytokines, while also suppressing the inhibitory activity of regulatory T cells (PubMed: 24591374). In oncology, OX40 is a prominent therapeutic target for agonistic agents designed to stimulate anti-tumor immunity. The specific modality of secreted Fc-OX40L refers to engineered fusion proteins or gene-therapy-delivered constructs that provide multivalent OX40 stimulation, mimicking the natural ligand's activity to enhance the effector function of tumor-infiltrating lymphocytes (PubMed: 29330111). These therapies, such as MEDI6383 or mRNA-encoded OX40L, are being investigated for their ability to turn cold tumors hot and are often combined with PD-1/PD-L1 inhibitors to achieve synergistic therapeutic effects (ClinicalTrials.gov: NCT02221960).

Other names

CD134TNFRSF4ACT35TXGP1LTax-transactivation-activated receptor

Agonism of the OX40 receptor provides a potent costimulatory signal to activated T cells, which enhances their proliferation, survival, and effector functions, such as cytokine production, while simultaneously inhibiting the suppressive activity of regulatory T cells (Tregs) within the tumor microenvironment.