Abstract 4472: A mouse model for GvHD: an excellent tool for evaluating the efficacy of anti-GvHD drugs and testing mechanisms of immunoregulation

Abstract

Abstract Hematological malignancies, including leukemia, lymphoma and multiple myeloma, account for about 7% of all newly diagnosed cancers. Allogeneic hematopoietic stem cell transplantation (HSCT) is a traditional treatment for hematologic malignancies. Currently, CAR-T cell therapy has made a major breakthrough in the treatment of hematologic malignancies. However, the occurrence of acute Graft-versus-Host Disease (GvHD) represents a major obstacle for HSCT and limits the application of CAR-T cell therapy. GemPharmatech established and characterized two murine models for anti-GvHD drug evaluation. In the first model, bone marrow from C57BL/6 donor mice was transplanted into a sublethally-irradiated BALB/c recipient mouse. In this model, T cell infiltration, tissue damage, and systemic inflammation were observed, similar to the clinical observations of patients receiving allogeneic HSCT. Efficacy evaluation of anti-GVHD drugs have been carried out based on this model. Our results showed that treatment with the anti-GVHD drug Ibrutinib, the survival rate and the lifespan of the mice was significantly prolonged, and the GvHD score was reduced by about 70% compared with the placebo group. In the second model, human Peripheral Blood Mononuclear cells (PBMCs) were transplanted into irradiated severe immunodeficient NCG mice. The cohort was irradiated to accelerate GvHD occurrence. The reconstructed human T cells will recognize and attack mouse tissues to cause GvHD. Our results showed that hCD45+ cells infiltrated into heart, liver, and spleen of huPBMC-NCG mice. This model has also been successfully used for anti-GvHD efficacy evaluation. Upon treatment with an anti-GVHD drug, the lifespan of huPBMC-NCG mice was significantly extended and weight loss was alleviated. Overall, the above-mentioned GvHD models show great potential for preclinical evaluation of anti-GvHD drug development in allogeneic HSCT. Citation Format: Meirong Wu, Shiru Zhang, Fang Zhu, Hongyan Sun, Jianming Xu, Cunxiang Ju, Hongyu Wang, Santi Suryani Chen, Zhiying Li, Mark Wade Moore, Jing Zhao, Xiang Gao. A mouse model for GvHD: an excellent tool for evaluating the efficacy of anti-GvHD drugs and testing mechanisms of immunoregulation. [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 4472.