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.

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 homozygous B-hCD27 mice.

Strain specific CD27 expression analysis in wild-type mice and homozygous B-hCD27 mice by flow cytometry.
Splenocytes were collected from WT and homozygous B-hCD27 mice stimulated with anti-CD3ε in vivo , and analyzed by flow cytometry with species-specific anti-CD27 antibodies. Mouse CD27 was detectable in WT and homozygous B-hCD27 mice. Human CD27 was exclusively detectable in homozygous B-hCD27 mice but not WT mice. This might be due to cross-recognition of hCD27 by anti-mCD27 antibodies.

Antitumor activity of anti-human CD27 antibodies in B-hCD27 mice.
(A) Anti human CD27 antibodies inhibited MC38 tumor growth in 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 tumor volume reached approximately 100 mm³, at which time they were treated with anti-human CD27 antibodies with doses and schedules indicated in panel. (B) Body weight changes during treatment. As shown in panel A, anti-human CD27 antibodies were efficacious in controlling tumor growth in B-hCD27 mice, demonstrating that the 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 anti-human CD27 antibodies in B-hCD27 mice.
(A) Anti human CD27 antibodies inhibited MC38 tumor growth in B-hCD27 mice. Murine colon cancer MC38 cells (5×10⁵) were subcutaneously implanted into homozygous B-hCD27 mice (male, 6 week-old, n=5). Mice were grouped when tumor volume reached approximately 100 mm³, at which time they were treated with anti-human CD27 antibodies with doses and schedules indicated in panel. (B) Body weight changes during treatment. As shown in panel A, anti-human CD27 antibodies were efficacious in controlling tumor growth in B-hCD27 mice, demonstrating that the B-hCD27 mice provide a powerful preclinical model for in vivo evaluation of anti-human CD27 antibodies. Values are expressed as mean ± SEM.