Abstract 1694: Validation of GVHD in humanized mouse model for preclinical efficacy screen

Abstract

Abstract Bone marrow transplantation has been successfully and widely used to treat diseases such as leukemia and lymphoma. However, the complication Graft vs Host Disease (GVHD) is a serious hindrance in patients' outcome. Immunosuppressant such as Cyclosporine A has been used to decrease the GVHD occurrence, but the associated side-effect such as transplant rejection and opportunistic infection outweigh its benefit. Therefore, new medication to suppress GVHD without severe toxicity is urgently in need now. To build better preclinical platform for drug efficacy evaluation in GVHD, we have validated the GVHD model in both mouse host and humanized mouse host. We collected bone marrow cells and splenocyte from C57BL/6J (H-2d) mice and transplant to irradiated BALB/c (H-2b) mice to induce GVHD. In humanized model, we injected humanized NPI mice (NOD-Prkdcscid-Il2rgem1lDMO with CD34+ hematopoeitc stem cells (HSCs) reconstitution) with PBMCs from MHCII mismatched donors to trigger GVHD occurrence. In both models, we observed the typical clinical symptoms such as hollow back, inactiveness, body weight loss in transplanted mice. Humanized mice with transplantation start to die in 2 weeks. In the endpoint, we used FACS to analyze the cell population change in whole blood, spleen and lymph nodes, and found histological changes in GI tract and skin. Thus, this model is suitable to screen potential human-specific antibodies or new small molecules. We are also going to explore extra parameters to characterize the disease progression. Citation Format: Menglin Liu, Yingying Cai, Na Xu, Ya Zhang, Rou Xie, Lijun Jia, Qing Lin. Validation of GVHD in humanized mouse model for preclinical efficacy screen [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 1694.