B-hTNFRSF4 (OX40) mice

Basic Information

Strain Name
C57BL/6-Tnfrsf4tm1( TNFRSF4)Bcgen/Bcgen
Stock Number
110014
Common Name
B-hTNFRSF4(OX40) Mice
Source/Investigator
Bcgen (Beijing Biocytogen Co., Ltd)
Related Genes
Tnfrsf4 (tumor necrosis factor receptor superfamily, member 4)
Species
C57BL/6
Appearance
Black
Genotypes
Homozygous

Description

OX40, also known as Tnfrsf4 (Tumor necrosis factor receptor super family, member 4), is mainly expressed on the surface of activated CD4 + and CD8 + T cells, and its binding with the OX40 ligand can stimulate CD8 + T cell activation. The coactivation of OX40/OX40L enhances T cell function, including cytokine production, proliferation and T cell survival. An OX40 agonist can reduce Regulatory T cells (Tregs) and improve anti-tumor activity.

Targeting Strategy

Details

Phenotype

Protein Expression Analysis

Strain specific OX40 expression analysis in homozygous B-hOX40 mice by flow cytometry.

Splenocytes were collected from WT and homozygous B-hOX40 (H/H) mice stimulated with anti-CD3ε in vivo (7.5 μg/mice), and analyzed by flow cytometry with species-specific anti-OX40 antibody. Mouse OX40 was exclusively detected in WT mice. Human CD40 was exclusively detected in homozygous B-hOX40 but not WT mice.

Application

In vivo efficacy of anti-human OX40 antibody

Antitumor activity of anti-human OX40 antibodies in B-hOX40 mice.

(A) Anti-human OX40 antibodies inhibited MC38 tumor growth in B-hOX40 mice. Murine colon cancer MC38 cells (5ⅹ105) were subcutaneously implanted into heterozygous B-hOX40 mice (female, 4-6 week-old, n=5). Mice were grouped when tumor volume reached approximately 100 mm3, at which time they were treated with anti-human OX40 antibody with different doses and schedules indicated in panel (B) Body weight changes during treatment. As shown in panel A, anti-human CD40 antibodies were efficacious in controlling tumor growth in B-hOX40 mice, demonstrating that the B-hOX40 mice provide a powerful preclinical model for in vivo evaluation of anti-human OX40 antibodies. Values are expressed as mean ± SEM

Antitumor activity of anti-human OX40 antibody in B-hOX40 mice.

(A) Anti-human OX40 antibody inhibited MC38 tumor growth in B-hOX40 mice. Murine colon cancer MC38 cells (5ⅹ105) were subcutaneously implanted into homozygous B-hOX40 mice (female, 4-6 week-old, n=5). Mice were grouped when tumor volume reached approximately 100 mm3, at which time they were treated with anti-human CD40 antibody and schedules indicated in panel (B) Body weight changes during treatment. As shown in panel A, anti-human OX40 antibody was efficacious in controlling tumor growth in B-hOX40 mice, demonstrating that the B-hOX40 mice provide a powerful preclinical model for in vivo evaluation of anti-human OX40 antibodies. Values are expressed as mean ± SEM

In vivo efficacy of MOXR0916 (in house)

Antitumor activity of anti-human OX40 antibody in B-hOX40 mice.

(A) Anti-human OX40 antibody inhibited MC38 tumor growth in B-hOX40 mice. Murine colon cancer MC38 cells (5ⅹ105) were subcutaneously implanted into homozygous B-hOX40 mice (female, 4-6 week-old, n=6). Mice were grouped when tumor volume reached approximately 150±50 mm3, at which time they were treated with anti-human OX40 antibody with different doses and schedules indicated in panel (B) Body weight changes during treatment. As shown in panel A, anti-human CD40 antibody was efficacious in controlling tumor growth in B-hOX40 mice, demonstrating that the B-hOX40 mice provide a powerful preclinical model for in vivo evaluation of anti-human OX40 antibodies. Values are expressed as mean ± SEM

Antitumor activity of anti-human OX40 antibody in B-hOX40 mice.

(A) Anti-human OX40 antibody inhibited MC38 tumor growth in B-hOX40 mice. Murine colon cancer MC38 cells (5ⅹ105) were subcutaneously implanted into homozygous B-hOX40 mice (female, 4-6 week-old, n=6). Mice were grouped when tumor volume reached approximately 150±50 mm3, at which time they were treated with anti-human OX40 antibody with different doses and schedules indicated in panel (B) Body weight changes during treatment. As shown in panel A, anti-human CD40 antibody was efficacious in controlling tumor growth in B-hOX40 mice, demonstrating that the B-hOX40 mice provide a powerful preclinical model for in vivo evaluation of anti-human OX40 antibodies. Values are expressed as mean ± SEM

References

1. J Immunol. 2013 Oct 1;191(7):3641-50. doi:10.4049/jimmunol.1202752. Epub 2013 Sep 6.
2. Cancer Res. 2013 Dec 15;73(24):7189-7198.doi: 10.1158/0008-5472.CAN-12-4174. Epub 2013 Oct 31.
3. Clin Cancer Res. 2013 Mar 1;19(5):1044-53.doi: 10.1158/1078-0432.CCR-12-2065.
4. Annu Rev Immunol. 2010;28:57-78. doi: 10.1146/annurev-immunol-030409-101243.

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