Therapeutics: OX40 ligand (OX40L; CD134L)
Patient sample and mouse studies suggest inhibiting OX40L could help treat systemic sclerosis. In patient skin and serum samples, OX40L levels were higher than in samples from healthy volunteers. In a mouse model of systemic sclerosis, OX40L knockout decreased levels of pro-inflammatory cytokines and infiltration of macrophages and T cells in the skin and decreased inflammation-induced fibrosis in the skin, lungs and blood vessels compared with normal OX40L expression. Also in the model, an anti-OX40L antibody decreased skin thickness and the number of myofibroblasts in the skin compared with a control antibody. In a second mouse model of systemic sclerosis, the anti-OX40L antibody decreased fibrosis in the lung. Next steps could include testing OX40L inhibition in models of other fibrotic diseases.
AstraZeneca plc and AgonOx have MEDI-6469, a murine anti-OX40 mAb, in Phase I/II testing to treat prostate cancer and in Phase I testing to treat solid tumors. ...