Abstract 5178: Humanized OX40/OX40L mice as a tool for evaluating novel therapeutics

The use of immune-competent mouse models that express target human genes provide a promising preclinical platform aimed at developing novel immunotherapies. Emerging immunotherapies include targeting OX40 and OX40 ligand (OX40L), which can lead to enhanced T cell activation, proliferation, and effector function. Blocking the OX40/OX40L pathway improves autoantigen-specific T cell responses and decreases immunocompetence across several autoimmune diseases. To explore the potential of OX40 and OX40L antibody efficacy studies, we developed double humanized B-hOX40/hOX40L mice by replacing the extracellular domain sequences of murine Ox40 and Ox40l with the corresponding human sequences. We validated human OX40L gene expression by RT-PCR and OX40/OX40L protein expression by flow cytometry in B-hOX40/hOX40L mice. Additionally, percentages of splenic, blood, and lymph node immune cells were similar between B-hOX40/hOX40L and wild-type C57BL/6 mice. Altogether, this data demonstrates that B-hOX40/hOX40L mice are suitable for in vivo efficacy studies using anti-human OX40 and OX40L antibodies. Citation Format: Chonghui Liu, Jiawei Yao, Xiaofei Zhou, James Jin, Zan Zhang. Humanized OX40/OX40L mice as a tool for evaluating novel therapeutics. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5178.