Basic Information

Strain Name
C57BL/6-Havcr2tm1(HAVCR2)Bcgen/Bcgen
Stock Number
110018
Common Name
B-hTIM3 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.

Publications using B-hTIM3 mice

  1. Zhang D, Jiang F, Zaynagetdinov R, Huang H, Sood VD, Wang H, Zhao X, Jenkins MH, Ji Q, Wang Y, Nannemann DP, Musil D, Wesolowski J, Paoletti A, Bartholomew T, Derner MG, An Q, Iffland C, Halle JP. Identification and characterization of M6903, an antagonistic anti-TIM-3 monoclonal antibody. Oncoimmunology. 2020 Apr 1;9(1):1744921. doi: 10.1080/2162402X.2020.1744921. PMID: 32313722; PMCID: PMC7153820.

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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