B-hCD27 mice

Basic Information

Gene targeting strategy

Gene targeting strategy for B-hCD27 mice. The exons 1-5 of mouse Cd27 gene that encode the extracellular domain were replaced by human CD27 exons 1-5 in B-hCD27 mice.

mRNA expression analysis

Strain specific analysis of CD27 gene expression in WT and homozygous B-hCD27 mice by RT-PCR.

Mouse Cd27 mRNA was detectable only in splenocytes of wild-type mice. Human CD27 mRNA was detectable only in B-hCD27 mice.

Protein expression analysis

Species-specific CD27 protein expression analysis in humanized B-hCD27 mice. Following anti-CD3ε stimulation in vivo, splenocytes were isolated from wild-type (WT) and homozygous B-hCD27 mice and analyzed by flow cytometry using species-specific anti-CD27 antibodies. Murine CD27 protein was detected in wild-type and B-hCD27 mice, due to the cross-reactivity of the antibody, while human CD27 protein was exclusively detected in B-hCD27 mice.

In vivo efficacy of anti-human CD27 antibodies

Antitumor activity of an anti-human CD27 antibody in humanized B-hCD27 mice. Murine colon cancer MC38 cells (5×10⁵) were subcutaneously implanted into heterozygous B-hCD27 mice (male, 4-6 week-old, n=5). Mice were grouped when the tumor volume reached approximately 100 mm³, at which time they were treated with either a vehicle control or an anti-human CD27 antibody at doses and schedules as indicated. (A) The anti-human CD27 antibody inhibited MC38 tumor growth in B-hCD27 mice, (B) without negatively impacting body weight changes during treatment. B-hCD27 mice provide a powerful preclinical model for in vivo evaluation of anti-human CD27 antibodies. Values are expressed as mean ± SEM.

 

Antitumor activity of an anti-human CD27 antibody in humanized B-hCD27 mice. Murine colon cancer MC38 cells were subcutaneously implanted into homozygous B- hCD27 mice. Mice were divided into control and treatment groups (n=5) when the tumor size was approximately 150±50 mm³. Anti-hCD27 antibody (varlilumab) significantly inhibited tumor growth in homozygous B-hCD27 mice, suggesting that the B-hCD27 mouse model is an effective tool for in vivo hCD27 antibody efficacy studies. (A) Tumor average volume ± SEM, (B) Mice average body weight ± SEM.

References

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