PD-1 (Programmed death-1) is mainly expressed on the surface of T cells and primary B cells. The two PD-1 ligands, PD-L1 and PD-L2, are widely expressed on antigen-presenting cells (APCs). PD-1 interacts with its ligands and plays an important role in the negative regulation of the immune response. PD-L1 protein expression is detected in many human tumor tissues. PD-L1 expression in tumor cells could be induced by the microenvironment of tumor cells. PD-L1 expression is favorable for tumorigenesis and growth, for induction of anti-tumor T Cell Apoptosis, and for escaping responses by the immune system. Inhibition of PD-1 binding to its ligand can result in tumor cells that are exposed to the killing version of the immune system, and thus is a target for cancer treatments.
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-hPD-1/hCD27 mice . The exon 2 of mouse Pdcd1 gene that encode the extracellular domain were replaced by human PD-1 exon 2, The exons 1-5 of mouse Cd27 gene that encode the extracellular domain were replaced by human CD27 exons 1-5 in B-hPD-1/hCD27 mice.
Protein Expression Analysis
Strain specific CD27 expression analysis in homozygous B-hPD-1/hCD27 mice by flow cytometry. Splenocytes were collected from WT and homozygous B-hPD-1/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 B-hPD-1/hCD27 mice. Human CD27 were exclusively detectable in B-hPD-1/hCD27 mice but not WT mice. This might result from the cross-recognition of hCD27 by anti-mCD27 antibodies.
Strain specific PD-1 expression analysis in homozygous B-hPD-1/hCD27 mice by flow cytometry. Splenocytes were collected from WT and homozygous B-hPD-1/hCD27 mice stimulated with anti-CD3ε in vivo, and analyzed by flow cytometry with species-specific anti-PD-1 antibody. Mouse PD-1 was exclusively detectable in WT mice. Human PD-1 were exclusively detectable in B-hPD-1/hCD27 mice but not WT mice.
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