SITC 2022 Poster 950

TNFR2 HuGEMM™ Mouse Model for Evaluation of hTNFα-hTNFR2 Signaling Effect on iTreg Differentiation

Xuefei Yan, Danting Yan, Jie Lin, Lei Zheng , Jessie Wang, Annie An, Xiaoxi Xu, Demi X. Liu

Peripheral induced regulatory T cells (iTreg) play an important role for immune homeostasis. Dysregulation of iTreg differentiation is frequently associated with autoimmune diseases or tumors. Tumor necrosis factor (TNF) α is a pleiotropic cytokine with multiple biological function. Some studies suggest that mouse TNFα inhibits the differentiation of iTregs via TNFR2, providing TNFα-TNFR2 as an attractive target for drug development, for potential control of various diseases including malignant tumors and autoimmune diseases.

However, whether human TNFα-TNFR2 signaling pathway plays similar role on iTreg differentiation remains unknown. Moreover, no optimal animal model is currently available for candidate drug evaluation targeting human TNFα-TNFR2. In this study, a humanized TNFR2 mouse model (TNFR2 HuGEMM) was developed to evaluate the effect of human TNFR2 agonist or antagonist on iTreg differentiation, which may be useful in the development of immunotherapies to treat tumors or autoimmune diseases, respectively.

• Importance of TNFα-TNFR2 signaling pathway iTreg differentiation
  
  
• Confirmation of the expression of humanized TNFR2
  
  
• hTNFα and the suppressive function of iTreg on CD3⁺ T cell proliferation

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