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B-hCD40 mice

2017-08-04 13:31:34.0

Strain description

Strain NameC57BL/6-Cd40tm1(hCD40)/BcgenCommon NameB-hCD40 mice
BackgroundC57BL/6Catalog numberB-CM-020
Catalog number (Males)BCM020MCatalog number (Females)BCM020F
Related GenesCd40 (CD40 antigen)

Gene Description

CD40 (cluster of differentiation 40) is a tumor necrosis factor receptor superfamily member expressed on APC such as dendritic cells (DC), B cells, and monocytes as well as many non-immune cells and a wide range of tumors. Interaction with its trimeric ligand CD154 on activated T helper cells results in APC activation, which has been found to be essential in mediating a broad variety of immune and inflammatory responses including T cell-dependent immunoglobulin class switching, memory B cell development, and germinal center formation. Agonistic CD40 mAb have been shown to activate APC and promote anti-tumor T cell responses and to foster cytotoxic myeloid cells with the potential to control cancer in the absence of T-cell immunity. Thus, agonistic CD40 mAb may serves as a new antitumor  drugs which are fundamentally different from mAb which block negative immune checkpoint such as anti-CTLA-4 or anti-PD-1.


Targeting strategy


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mRNA expression analysis


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Fig 1. RT-PCR analysis of the CD40 gene. 

The mCD40 mRNA was detected in both wild type C57BL/6 and heterozygous B-hCD40 mice, while the hCD40 mRNA was detected only in the heterozygous B-hCD40 mice.




Protein expression analysis

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Fig 2. Splenocytes from both wild type (WT) C57BL/6 and heterozygous B-hCD40 mice were analyzed by flow cytometry. 

Mouse CD40+ B cells were detected in both WT C57BL/6 and heterozygous B-hCD40 mice, while human CD40+ B cells were only detected in the heterozygous B-hCD40 mice.




CD40 Abs efficacy evaluation

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Fig 3. Murine colon cancer MC38 cells were subcutaneously implanted into heterozygous B-hCD40 mice. Mice were grouped when the tumor size was approximately 150±50mm3 (n=5). Three human CD40 antibodies differently inhibited tumor growth, confirming that the B-hCD40 mouse model is a powerful tool for in vivo CD40 antibody pharmacological efficacy studies. A. Tumor average volume ± SEM. B. Mice average weight ± SEM.


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Fig 4. Murine colon cancer MC38 cells were subcutaneously implanted into homozygous B-hCD40 mice. Mice were grouped when the tumor size was approximately 150±50mm3 (n=5). Human CD40 antibody significantly inhibited tumor growth, confirming that the B-hCD40 mouse model is a powerful tool for in vivo CD40 antibody pharmacological efficacy studies. A. Tumor average volume ± SEM. B. Mice average weight ± SEM.

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