Basic Information
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Targeting strategy
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Gene targeting strategy for B-NDG HLA-2.1 mice. The B2m gene (Exon1 to Exon3) of mouse was replaced by the sequence encompassing the human B2M CDS and HLA-A2.1 gene in B-NDG HLA-2.1 mice. The mouse B2m gene was knocked out while a fused gene composed of mouse B2m and Fcgrt gene was inserted after the signal peptide sequence of mouse Fcgrt gene in B-NDG B2m KO mice plus. The B-NDG HLA-2.1 mice were mated with B-NDG B2m KO mice plus to obtain a new mouse strain named B-NDG hB2M/HLA-A2.1 mice plus.
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Determination of plasma concentrations of human IgG in different mice
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Pharmacokinetic characteristic of B-NDG hB2M/HLA-A2.1 mice plus has no difference compared with B-NDG mice.
B-NDG mice, B-NDG HLA-A2.1 mice, B-NDG hB2M/HLA-A2.1 mice plus were treated with YH001 (anti-human CTLA4 antibody) (n=4). Blood samples were collected at different time point for the PK assay. The results showed that the PK results of B-NDG hB2M/HLA-A2.1 mice plus group was similar to that in B-NDG mice, and the drug concentration of B-NDG HLA-A2.1 mice group could not be measured at the time point 4 days later. Results indicated that when compared with B-NDG HLA-A2.1 mice, the B-NDG hB2M/HLA-A2.1 mice plus can significantly extend the half-life of antibody drugs in mice.
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Summary
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Determination of plasma concentrations of human IgG in different mice.
Compared with B-NDG HLA-A2.1 mice, the B-NDG hB2M/HLA-A2.1 mice plus can significantly extend the half-life of antibody drugs in mice.
