Abstract 2733: Developing novel anti-OX40 antibodies on Biocytogen's in vivo drug screening platform

Abstract

Abstract OX40, also known as CD134 or TNFRSF4, is a member of the TNFR superfamily of receptors. OX40 is a co-stimulatory receptor, and it interacts with its ligand to providepositive signal for T cell activation. OX40 is not expressed on resting naïve T cells, however its expression goes up after 24 to 72 hours following activation. Disruption of OX40 pathway led to defective T cell responses and overexpression of OX40 caused massive immune activation. Due to its importance in keeping immune homeostasis, strategies modulating the OX40 pathway hold great promise in fighting against cancer and autoimmune diseases. We have interests in developing novel OX40 antibodies for boosting cancer patients' own immunityinlight of other successful immune checkpoint modulators. We developed a cohort of OX40 specific antibodies using the classic hybridoma technology. In order to screen their efficacy to stimulate anti-tumor activity in live animals, we managed to rank these antibodies using Biocytogen'shumanized mouse platform of immune checkpoints. Specifically, we utilized humanized OX40 mice (h-OX40) and implanted syngeneic tumors subcutaneously, followed by treating mice with purified testing antibodies. Via this approach, we are able to discern several lead antibodies that effectively inhibited tumor growth without prior knowledge of their in vitro activities. Furthermore, we identified that one clone works in concert with Keytruda in the dual humanized model of h-OX40 and h-PD1. We are currently investigating the mechanisms of action underlying these potentially useful antibodies. Citation Format: Chaoshe Guo, Yanan Guo, Yuelei Shen, Benny Yang. Developing novel anti-OX40 antibodies on Biocytogen's in vivo drug screening platform [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 2733.