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Animal Models and Cell Lines

>Single Humanized Immune-Checkpoint Mice

TNFRSF9 (TNF receptor super family member 9), also called CD137 or 4-1BB, is mainly expressed on the surface of activated T, NK,and mononuclear cells. CD137 is activated by its ligand CD137L or an activating CD137 monoclonal antibody, and stimulates T cell activation, proliferation and cytokine production.

Strain description

 

Strain Name

C57BL/6-Tnfrsf9tm1(hTNFRSF9)/Bcgen

Common Name

B-hTNFRSF9(4-1BB) mice

Background

C57BL/6

Catalog number

B-EM-023

Catalog number (Males)

BEM023M

Catalog number (Females)

BEM023F

Related Genes

Tnfrsf9 (tumor necrosis factor receptor superfamily, member 9)


Gene description

 

TNFRSF9 (TNF receptor super family member 9), also called CD137 or 4-1BB, is mainly expressed on the surface of activated T, NK,and mononuclear cells. CD137 is activated by its ligand CD137L or an activating CD137 monoclonal antibody, and stimulates T cell activation, proliferation and cytokine production. This co-stimulatory signal can also multiply antigen presenting cells and result in cell factor secretion. Experiments show that CD137 co-stimulation regulates T cell and antigen presenting cell function for antitumor immunity, providing new targets for tumor immunological therapies.

mRNA expression verification

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Fig 1. RT-PCR analysis of 4-1BB gene.

The h4-1BB, but not m4-1BB, mRNA was detected in splenocytes of the homozygous B-h4-1BB mice.


Protein expression analysis

1535507357138515.png

Fig 2. Spleen cells from both wild type (WT) C57BL/6 and the B-h4-1BB homozygous mice were analyzed by flow cytometry. 

Mouse 4-1BB+ T cells were detected in the WT mice, while human 4-1BB+ T cells were detected in the homozygous B-h4-1BB  mice.


4-1BB Abs efficacy evaluation

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Fig 3. Murine colon cancer MC38 cells were subcutaneously implanted into heterozygous B-h4-1BB mice.

Mice were divided into control and treatment groups (n=5), which included 2 antibodies at 2 doses, tested when the tumor size was approximately 100 mm3. Anti-h4-1BB antibody Ab2 showed significant inhibitory effects at both doses, while Ab1 only inhibited tumor growth at the higher dose for heterozygous B-h4-1BB mice, suggesting that B-h4-1BB mouse model is a useful tool for in vivo h4-1BB antibody efficacy studies. (A) Tumor average volume ± SEM, (B) Mice average weight ± SEM.



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