OX40 (agonist)

Class

Agonist anti-OX40 monoclonal antibody (revdofilimab)

Pathway

TNF receptor superfamily costimulatory pathway; activates effector T cells and inhibits suppressive activity of regulatory T cells

Notes

original target text: OX40 (TNFRSF4)

OX40 (also known as TNFRSF4) is a costimulatory receptor belonging to the tumor necrosis factor (TNF) receptor superfamily, expressed transiently on the surface of activated T cells. Its natural ligand, OX40L, is displayed on antigen-presenting cells such as dendritic cells during immune activation. Engagement of OX40 delivers a second signal that reinforces T-cell receptor signaling, promoting the survival, proliferation, and effector function of activated CD4+ and CD8+ T cells. OX40 signaling also modulates regulatory T cells (Tregs), the subset that normally restrains immune responses; agonism can reduce Treg suppressive capacity, shifting the balance of an immune response toward active effector immunity. Because of this dual effect, agonist antibodies and other agonist molecules directed at OX40 are being explored as a way to amplify anti-tumor immune responses, particularly in cancers where T cells are present but functionally suppressed by the tumor microenvironment. The same pathway is relevant, in the opposite direction, to autoimmune and inflammatory disease, where blocking OX40-OX40L interactions can dampen pathological T-cell activity. The mechanism sits within the broader class of costimulatory pathway modulation, alongside related TNF receptor superfamily members such as CD40 and 4-1BB, that collectively shape the strength and duration of adaptive immune responses.