TNFRSF1B

Humanized Gene Knock-in Strategy

Chimeric cDNA：human exon2-exon6 & mouse exon7-10

Humanized TNFRSF1B Protein Sequence

Validation of hTNFRSF1B (TNFR2) Expression in the Immune Cells from Spleen of Humanized TNFRSF1B Mice

Figure 1. The expression of human TNFRSF1B in humanized TNFRSF1B mice was measured by FACS. In humanized TNFRSF1B mice, active expression of human TNFRSF1B was detected in Treg cells and Neutrophils isolated from spleen. (Data in partnership with collaborators)

Validation of hTNFRSF1B (TNFR2) Expression in the Immune Cells from the Peripheral Blood of Humanized TNFRSF1B Mice

Figure 2. The expression of human TNFRSF1B in humanized TNFRSF1B mice was measured by FACS. In humanized TNFRSF1B mice, active expression of human TNFRSF1B was detected in Treg cells and Neutrophils isolated from peripheral blood cells. (Data in partnership with collaborators)

Validation of hTNFRSF1B (TNFR2) Expression in the Immune Cells from the Lymph Nodes of Humanized TNFRSF1B Mice

Figure 3. The expression of human TNFRSF1B in humanized TNFRSF1B mice was measured by FACS. In heterozygous humanized TNFRSF1B mice, active expression of human TNFRSF1B was detected in Treg cells isolated from Lymph node. (Data in partnership with collaborators) 

In vivo Efficacy Evaluation of Anti-hTNFR2 in TNFR2 HuGEMM Mice with MC38-OVA Tumors

Figure 4. In vivo anti-tumor effect of anti-TNFRSF1B antibody, in a humanized mouse model of TNFRSF1B In vivo validation of anti-tumor efficacy in a MC38-OVA tumor-bearing model of humanized TNFRSF1B mice. Homozygous humanized TNFRSF1B mice were inoculated with MC38 colon cancer cells. The drug targeting human TNFRSF1B, showed a very significant anti-tumor effect, demonstrating that the humanized TNFRSF1B mice are a good in vivo model for validating the efficacy of antibodies targeting human TNFRSF1B. (Data in partnership with collaborators)

FACS for Blood upon TNFR2 Antagonist Treatment

Figure 5. FACS for blood upon TNFRSF1B antagonist treatment. Addition of antagonistic hTNFRSF1B antibody can impair hTNF-induced Treg cells proliferation, while the agonistic hTNFRSF1B antibody alone can induce a modest proliferative response. (Data in partnership with collaborators)

TIL Analysis upon TNFR2 Antagonist Treatment

Figure 6. TIL analysis upon TNFR2 antagonist treatment.

1 tumor in hTNFR2 Ab1 treatment group decreased  (1/7, TV=0)

2 tumors in hTNFR2 Ab2 treatment group decreased  (2/7, TV=0; 3/7 died during dosing period)

(Data in partnership with collaborators)

TNFR2 Antagonists can restore the T cell balance by eliminating Treg and activating Teff in tumor microenvironment

Figure 7.  TNFRSF1B blockade increases the Teff/Treg ratios in tumor microenvironment. (Data in partnership with collaborators)