OX40 (also known as CD134)

OX40(also called CD134) has OX40L, or CD252, as its ligand. Like CD27, OX40 promotes the expansion of effector and memory T cells, however it is also noted for its ability to suppress the differentiation and activity of T-regulatory cells, and also for its regulation of cytokine production. OX40's value as a drug target primarily lies it the fact that, being transiently expressed after T-cell receptor engagement, it is only upregulated on the most recently antigen-activated T cells within inflammatory lesions. Anti-OX40 monoclonal antibodies have been shown to have clinical utility in advanced cancer.

Background


OX40 belongs to the tumor necrosis factor receptor family. It is mainly expressed on the activated lymphocyte surface. OX40 is an important co-stimulant molecule in the immune response, which can improve the immunosuppressive effect in tumor microenvironment. Enhancing the cytotoxicity of lymphocytes plays an important role in mediating the development of tumor immune response. OX40's value as a drug target primarily lies in the fact that, being transiently expressed after T-cell receptor engagement, it is only upregulated on the most recently antigen-activated T cells within inflammatory lesions. Anti-OX40 monoclonal antibodies have been shown to have clinical utility in advanced cancer.

Molecular Biological Characteristics of OX40

OX40 is also called CD134. OX40L(CD252)is the only ligand of OX40, mainly expressed on the surface of activated antigen presenting cells(APC)as well as natural killer cells and mast cells. In the process of immunomodulation, antigen presenting cells combined with T cells, and antigen peptide -MHC complex was presented to T cells to stimulate T cell activation. At the same time, the OX40L on the surface of APC combined with the costimulatory molecule OX40 on the surface of T cells, which promoted the activation of T cells as the second signal. OX40 has the same effect as CD27, and can promote the proliferation of effector cells and memory cells and regulate the activity of T cells and the production of cytokines.

Expression of OX40 in Human Tumor Samples and Single Drug Treatment of OX40 Antibody

OX40 was expressed on the surface of infiltrating lymphocytes in various tumor tissues, while OX40 was expressed on CD4 T cells in lymphoma, especially on the surface of tumor infiltrated Treg cells. It is suggested that OX40 can be used as a potential molecular marker for monitoring.

Activation of OX40 signaling pathway can enhance the activity of CD4+T cells and CD8+T cells, and inhibit the function of Treg. The activated antibodies targeting costimulatory molecules (such as OX40) on the surface of T cells can directly improve the effect function of T cells and neutralize the immunosuppressive effect of Tregs. It has been found that OX40 antibody plays an important role in the depletion of tumor infiltrating Treg. This effect is mainly achieved by antibody-dependent cell-media-ted cytotoxicity (ADCC) or antibody dependent cell-mediated phagocytosis (ADCP) by antibody dependent cell mediated cytotoxicity, as well as with bone marrow and N. The activation of FC γ receptor on the surface of K cells is related.

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Reference:

Du Ping, Liu Lihong.(2017).Research Progress of OX40, a New Target of tumor Immunotherapy. Chinese Journal of Microbiology and Immunology.37(3),240-243