Abstract 4559: KY-B602, a humanized anti-human OX40 antibody, enhances CD4+T cell activation and inhibits tumor growth in a syngeneic model

Abstract OX40, a member of the tumor necrosis factor (TNF) receptor superfamily, is mainly expressed on activated T cells. As a secondary costimulatory molecule, activated OX40 can increase effector T-cell survival, proliferation, and memory. Anti-OX40 monoclonal antibodies have shown anti-tumor efficacy. Recent preclinical studies further support the potential synergistic effects of agonist OX40 immunotherapy in combination with cancer vaccination or in sequential co-administration with PD1 antibody to revert PD1 resistance. Several anti-OX40 agonistic monoclonal antibodies are currently tested in early phase cancer clinical trials either in monotherapy or in combination with other immune modulators. KY-B602 is a novel humanized IgG1 anti-OX40 antibody under pre-clinical development. It was generated from hybridoma and humanized by CDR grafting and structure simulation. KY-B602 specifically binds to the extracellular domain of human OX40 with high affinity (KD = 5.1 nM, determined by Biacore). FACS study showed KY-B602 also binds to both human and cynomolgus monkey OX40 over-expressed on 293T cells (EC50 =4.6nM, EC50=6.1nM, respectively). Another, in HT1080 cell reporter assay, KY-B602 significantly increased IL-8 secretion through OX40 pathway. In addition, KY-B602 dose-dependently augmented IL-2 and IFN-gamma secretion from CD4+T cells, that were pre-stimulated with IL-2 and PHA. However, in FACS competition assay, KY-B602 did not affect OX40L binding to OX40, suggesting that KY-B602 binds to a different epitope with that of OX40L. Moreover, KY-B602 inhibits in vivo tumor growth in MC38 syngeneic model. In summary, the current data of KY-B602 support its potency for cancer therapy. Citation Format: feng hao, feng he, mingxuan ning, zhaoshuai bai, jinying ning. KY-B602, a humanized anti-human OX40 antibody, enhances CD4+T cell activation and inhibits tumor growth in a syngeneic model [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4559.