CD27 is a TNF receptor super family member. It is expressed on the surface of T and B cells, and its binding with CD70 provides a co-stimulatory signal for T and B cell proliferation and for B cells producing immunoglobulins. Treating mice with a CD27 agonist antibody effectively enhanced the antitumor immune response for lymphoma and B16 melanoma, providing putative targets for tumor immunotherapy.
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.
Protein Expression Analysis
Strain specific CD27 expression analysis in 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 antibody. Mouse CD27 was detectable in WT and homozygous B-hCD27 mice. Human CD27 was exclusively detectable in B-hCD27 homozygous but not WT mice. This might be due to cross-recognition of hCD27 by anti-mCD27 antibodies.
In vivo efficacy of anti-human CD27 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.
Murine colon cancer MC38 cells were subcutaneously implanted into homozygote 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 significantly inhibited tumor growth in homozygote 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 weight ± SEM.
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