B-hHAVCR2 (TIM3) mice

Basic Information

Strain Name
C57BL/6-Havcr2tm1(HAVCR2)Bcgen/Bcgen
Stock Number
110018
Common Name
B-hHAVCR2 (TIM3) Mice
Source/Investigator
Bcgen (Beijing Biocytogen Co., Ltd)
Related Genes
Havcr2 (hepatitis A virus cellular receptor 2)
Species
C57BL/6
Appearance
Black
Genotypes
Homozygous

Description

T-cell immunoglobulin domain and mucin domain-3 (TIM3) is an activation-induced inhibitory molecule involved in immune tolerance and T-cell exhaustion in chronic viral infection and cancers. TIM3 maturation and cell surface expression is facilitated by forming a heterodimeric interaction with CD66a. Co- blockade of CD66a and TIM3 enhanced anti-tumor immune responses and eliminated tumors in mouse colorectal cancer models.

Targeting Strategy

 

Details

Phenotype

Protein Expression Analysis

Strain specific TIM3 expression analysis in homozygous B-hTIM3 mice by flow cytometry.

Cells in ascites were collected from WT and homozygous B-hTIM3 (H/H) mice stimulated with anti-CD3ε in vivo, and analyzed by flow cytometry with species-specific anti-TIM3 antibody. Mouse Tim3 was exclusively detectable in non-T and non-B cells from WT mice. Human TIM3 was exclusively detectable in non-T and non-B cells from homozygous B-hTIM3 but not WT mice.

Strain specific TIM3 expression analysis in homozygous B-hTIM3 mice by flow cytometry.

Splenocytes were collected from WT and homozygous B-hTIM3 (H/H) mice stimulated with anti-CD3ε in vivo, and analyzed by flow cytometry with species-specific anti-TIM3 antibody. Mouse Tim3 was exclusively detectable in WT mice. Human TIM3 were exclusively detectable in homozygous B-hTIM3 but not WT mice.

 

Application

In vivo efficacy of anti-human TIM3 antibodies

Antitumor activity of anti-human TIM3 antibodies in B-hTIM3 mice.

 (A) Anti-human TIM3 antibodies inhibited MC38 tumor growth in B-hTIM3 mice. Murine colon cancer MC38 cells were subcutaneously implanted into homozygous B-hTIM3 mice (male, 7 week-old, n=5). Mice were grouped when tumor volume reached approximately 100 mm3, at which time they were treated with anti-human TIM3 antibody with doses and schedules indicated in panel A. (B) Body weight changes during treatment. As shown in panel A, anti-human TIM3 antibody was efficacious in controlling tumor growth in B-hTIM3 mice, demonstrating that the B-hTIM3 mice provide a powerful preclinical model for in vivo evaluation of anti-human TIM3 antibodies. Values are expressed as mean ± SEM.

In vivo efficacy of anti-human TIM3 antibodies

Antitumor activity of anti-human TIM3 antibodies in B-hTIM3 mice.

(A) Anti-human TIM3 antibodies inhibited MC38 tumor growth in B-hTIM3 mice. Murine colon cancer MC38 cells were subcutaneously implanted into homozygous B-hTIM3 mice (female, 4 week-old, n=5). Mice were grouped when tumor volume reached approximately 100 mm3, at which time they were treated with two anti-human TIM3 antibodies with doses and schedules indicated in panel (B) Body weight changes during treatment. As shown in panel A, anti-human TIM3 Ab2 was efficacious in controlling tumor growth in B-hTIM3 mice, demonstrating that the B-hTIM3 mice provide a powerful preclinical model for in vivo evaluation of anti-human TIM3 antibodies. Values are expressed as mean ± SEM.

References

1. Nat Immunol. 2003 Nov;4(11):1102-10. Epub 2003 Oct 12.
2. Nat Immunol. 2005 Dec;6(12):1245-52. Epub 2005 Nov 13.
3. Immunity. 2007 Mar;26(3):311-21.
4. J Immunol. 2010 Feb 15;184(4):1918-30. doi: 10.4049/jimmunol.0903059. Epub 2010
Jan 18.

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