OX40: targeted immunotherapy--implications for tempering autoimmunity and enhancing vaccines.
OX40 (CD134), a membrane-bound member of the tumor-necrosis-factor-receptor superfamily, is expressed primarily on activated CD4+ T cells. Recently, several groups have reduced clinical signs of autoimmunity in animal models by blocking the OX40-OX40-ligand interaction or depleting OX40+ T cells. By contrast, engagement of OX40 in the setting of active immunization has potent adjuvant properties, leading to enhanced cytokine production and increased numbers of antigen-specific memory T cells. These potent adjuvant effects lead to an enhancement of anti-tumor responses. OX40 has several unique features that make it a clinically relevant target. They include: (1) T cells isolated from a site of inflammation that express OX40 are T cells that have been stimulated recentlythrough the T-cell receptor in vivo; (2) OX40 is only expressed on T cells found at the site of inflammation, therefore, targeting this receptor does not interfere with the peripheral T-cell repertoire; and (3) the biological function of OX40 is limited primarily to effector CD4+ T cells, which are a major source of cytokines to induce and maintain ongoing immune responses.
Weinberg
Andrew D
AD
Earle A. Chiles Research Institute, Providence Portland Medical Center, Portland, OR 97213, USA. aweinberg@providence.org
D000818:Animals; D015551:Autoimmunity / Q000276:immunology*; D006801:Humans; D007167:Immunotherapy; D008562:Membrane Glycoproteins / Q000276:immunology; D053278:OX40 Ligand; D053262:Receptors, OX40; D018124:Receptors, Tumor Necrosis Factor; D013601:T-Lymphocytes / Q000276:immunology; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000276:immunology*; D014612:Vaccines / Q000276:immunology
D008562:Membrane Glycoproteins; D053278:OX40 Ligand; D053262:Receptors, OX40; D018124:Receptors, Tumor Necrosis Factor; C505716:TNFRSF4 protein, human; C089251:TNFSF4 protein, human; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; D014612:Vaccines