Earle A. Chiles Research Institute/Oregon Health and Science University, Portland, OR, USA
OX40 is a TNF-receptor family member that is expressed on activated CD4 and CD8 T cells as well as Tregs.On effector T cells OX40 acts as a potent costimulatory protein and when engaged increases proliferation, effector function, and survival.Our group initially showed that OX40 agonists (Ab or OX40L:Ig fusion protein) injected into tumor-bearing mice increases anti-tumor immunity and can lead to immune-mediated rejection of tumors.Based on the preclinical data a mouse anti-human OX40 agonist was tested in non-human primates showing potent immune stimulating properties, which led to a phase I clinical trial in late stage cancer patients. A review of the phase I clinical trial will be discussed and how those findings led to clinical trials with a humanized OX40 Ab conducted by MedImmune/AstraZeneca.Data will be presented regarding the results of the phase I trial and what patient populations will be targeted in future phase II studies.Preclinical analyses of immunotherapy agents that enhance the function of OX40 agonists in tumor-bearing mice will also presented.A review of the therapeutic potency and mechanism of action of these combinations will be discussed.
Credits: None available.
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