OX‐40 (CD134)

Targeting macrophages in the tumour environment to enhance the efficacy of αOX40 therapy

“…To determine the effect of arginase inhibition on the efficacy of aOX40 therapy, MCA205 tumour-bearing mice were treated at day 10 with aOX40 or control antibody and again 7 days later. Arginase enzyme activity was blocked with daily injections of the specific inhibitor NOHA over days [12][13][14][15][16][17][18][19]. aOX40 alone significantly delayed tumour growth (P < 0Á001), but few animals were tumour-free at the end of the experiment (Fig.…”

“…6cii-iv). To determine the effect of combination treatment on survival, MCA205 tumour-bearing mice were treated at day 10 and day 17 with aOX40 or control antibody with or without daily IL-12 and IL-18 over days [12][13][14][15][16][17][18][19]. Whereas treatment with either aOX40 alone or combined therapy with IL-12 and IL-18 enhanced survival (aOX40 P < 0Á001, IL-12 + IL-18 P < 0Á001), the combination of aOX40 with IL-12 and IL-18 significantly enhanced survival compared with either strategy alone (aOX40 + IL-12 + IL-18 P < 0Á05 versus aOX40, P < 0Á01 versus IL-12 + IL-18) (Fig.…”

“…[12][13][14][15][16] Expression of the ligand for OX40 is tightly associated with acute inflammation, and has been demonstrated at sites of psoriasis, 17 rheumatoid arthritis 18 and autoimmune demyelination. 19 Provision of agonistic antibodies to OX40 (aOX40) significantly enhances antigen-specific T-cell responses to soluble antigen 12,14 and to antigens expressed in cancer cell lines. 13 This suggests that the lack of OX40 signalling may be a limiting factor to generate optimal antigen-specific immune responses in vivo.…”

Role of effector T cells in multiple sclerosis

“…tumor or chronic viral infections. 4-1BB is essential for the induction of EAE (37), whereas OX-40 is not necessarily involved in initial induction of the disease as their deficiency did not result in complete protection from the disease, and instead mediates autoreactive T cell priming, migration and function indicating their role in later stage of the disease (38)(39)(40). It has been reported that 4-1BB co-stimulatory signals can cooperate with immune checkpoint inhibitor, such as Programmed Death Ligand 1 (PDL1), and in turn obstruct and augment cytotoxic CD8 + T cell response in chronic viral infection accordingly (41).…”