B-hTNFRSF9 (4-1BB) Mice

Basic Information

Strain Name
C57BL/6-Tnfrsf9tm1(TNFRSF9)Bcgen/Bcgen
Stock Number
110004
Common Name
B-hCD137 (4-1BB) Mice
Source/Investigator
Bcgen (Beijing Biocytogen Co., Ltd)
Related Genes
Tnfrsf9 (tumor necrosis factor receptor superfamily, member 9)
Species
C57BL/6
Appearance
Black
Genotypes
Homozygous

Description

TNFRSF9 (Tumor necrosis factor receptor super family, member9), also called CD137 and 4-1BB, is a co-stimulatory molecule and is mainly expressed on the surface of T, NK and mononuclear cells. CD137 is activated by itsligand CD137L or activating anti-CD137 antibodies, resulting in T cell activation, proliferation and cytokine production. CD137L is expressed on antigen presenting cells such as dendritic cells and macrophages and activated B cells. In vivo studies show that CD137 activation increases anti-tumor immune responses, providing a new target for immunotherapy

Targeting Strategy

B-hCD137(4-1BB)-Mice-targeting-strategy

Details

Phenotype

Protein Expression Analysis

B-hCD137(4-1BB)-Mice-details-protein-expression-analysis

Splenocytes from both wild type (WT)C57BL/6 and homozygous B-h4-1BB mice were analyzed by flow cytometry. T cells from WT mice express the murine 4-1BB+ while the human 4-1BB+ was detectable on T cells from B-h4-1BB homozygous mice

Application

Human 4-1BB mAb (Urelumab Analog) Efficacy Evaluation

B-hCD137(4-1BB)-Mice-details-Human-4-1BB-mAb-Urelumab-Analog-efficacy-evaluation

Murine colon cancer MC38 cells were subcutaneously implanted into homozygous B-h4-1BB mice. Mice were divided into control and treatment groups (n=6), when the tumor size was approximately 150±50 mm3. Three doses Urelumab showed substantially inhibitory effects in the homozygous B-h4-1BB mice, suggesting that B-h4-1BB mouse model is a useful tool for in vivo h4-1BB antibody efficacy study. The average ± SEM of tumor sizes are shown in the figure.

Human 4-1BB mAb (Urelumab Analog) Toxicity Evaluation

B-hCD137(4-1BB)-Mice-details-Human4-1BB-mAb-Urelumab-Analog-toxicity-evaluation

Anti-h4-1BB antibody was injected into homozygous B-h4-1BB mice. Human 4-1BB mAb(Urelumab Analog) were i.p. injected into homozygous B-h4-1BB mice. Blood were collected two days after the second treatment and analyzed by Blood Routine Test.

B-hCD137(4-1BB)-Mice-details-Human4-1BB-mAb-Urelumab-Analog-toxicity-evaluation1

B-hCD137(4-1BB)-Mice-details-Human4-1BB-mAb-Urelumab-Analog-toxicity-evaluation2

Anti-h4-1BB antibody was injected into homozygous B-h4-1BB mice. Blood were collected at study endpoint and analyzed by Blood Biochemical Test.

Human 4-1BB mAb (Utomilumab Analog) Efficacy Evaluation (MC38 Cell Line)

B-hCD137(4-1BB)-Mice-details-Human4-1BB-mAb-UtomilumabAnalog-efficacy-evaluation-MC38-cell-line

Murine colon cancer MC38 cells were subcutaneously implanted into homozygous B-h4-1BB mice. Mice were divided into control and treatment groups (n=5), when the tumor size was approximately 150±50 mm3. Two doses Utomilumab analog showed substantially inhibitory effects in the homozygous B-h4-1BB mice, (A) Tumor average volume ± SEM, (B) Mice average weight ± SEM.

Human 4-1BB mAb (Utomilumab Analog) Toxicity Evaluation

B-hCD137(4-1BB)-Mice-details-Human4-1BB-mAb-UtomilumabAnalog-toxicity-evaluation

The blood biochemical index was examined with anti-human 4-1BB antibody on B-h4-1BB mice at the termination of efficacy evaluation experiment

Pharmacodynamic Test Using B-h4-1BB Mice

B-hCD137(4-1BB)-Mice-details-Pharmacodynamic-test-using-B-h4-1BB-mice

Murine colon cancer MC38 cells were subcutaneously implanted into homozygous B-h4-1BB mice. Mice were divided into control and treatment groups (n=8) when the tumor size was approximately 150±50mm3 . Both two doses of human 4-1BB antibody significantly inhibited tumor growth, confirming that the B-h4-1BB mouse model is a powerful tool for in vivo 4-1BB antibody pharmacological efficacy studies. (A) Tumor
average volume ± SEM, (B) Mice average weight ± SEM.

Tumor Infiltrating Lymphocyte (TILs) Analysis

B-hCD137(4-1BB)-Mice-details-Tumor-infiltrating-lymphocyte-TILs-analysis

4-1BB Ab efficacy evaluation. Tumor cells are isolated at the endpoint of experiment, analyzed by flow cytometry.

Ratio of Tumor Infiltrating Lymphocyte (TILs)

B-hCD137(4-1BB)-Mice-details-Ratio-of-tumor-infiltrating-lymphocyte-TILs

4-1BB Ab efficacy evaluation. Tumor cells were isolated at the endpoint of experiment and analyzed by flow cytometry.

References

1. PLoS One. 2014 Jan 21;9(1): e86337. doi: 10.1371/journal.pone.0086337. eCollection 2014.
2. Front Oncol. 2015 Jun 8;5:117. doi: 10.3389/fonc.2015.00117. eCollection 2015.
3. Clin Transl Immunology. 2014 Aug 1;3(8): e22. doi: 10.1038/cti.2014.18. eCollection 2014 Aug.
4. J Immunol. 2002 Jun 1;168(11):5483-90.

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