Immunomodulatory Effects Of Ox40 Agonists In A Defined Antigen Challenge In Cynomolgus Macaques.

3086 Background: Immunomodulatory antibodies targeting specific T cell costimulatory pathways have shown great potential as cancer therapeutics. OX40 agonists can enhance T cell proliferation and survival and cause tumor regressions in mouse models. While initial evaluations of pharmacodynamic activity of these compounds in non-human primate models have relied on non-specific T cell proliferation readouts (Ki67), additional sensitive biomarkers of pharmacodynamic activity would add value in evaluating optimal dosing and timing of candidate therapeutics. Methods: In this study, we compared the in vivo activity in cynomolgus macaques of intravenously infused OX40 agonist MEDI6469 (9B12, a murine IgG1 antibody) and MEDI6383, a human OX40 ligand fusion protein consisting of a dimer of OX40L trimers held together by Fcγ domains that also agonizes the OX40 receptor. Antigen-specific responses were evaluated to respiratory syncytial virus soluble F (sF) protein, which was administered intramuscularly on the same...