|Strain Name||C57BL/6-Pdcd1tm1(PDCD1) Cd274tm1(CD274)Tnfrsf9tm1(TNFRSF9)/Bcgen||Common Name||B-hPD-1/hPD-L1/h4-1BB mice|
NFRSF9(TNF receptor superfamily member 9, also known as 4-1BB)
NCBI Gene ID
Gene targeting strategy for B-hPD-1/hPD-L1/h4-1BB mice.
The exon 2 of mouse PD-1 gene that encode the IgV domain were replaced by human PD-1 exon 2 in B-hPD-1/hPD-L1/h4-1BB mice. The exon 3 of mouse Pd-l1 gene that encode the IgV domain were replaced by human PD-L1 exon 3 in B-hPD-L1/hPD-L1/h4-1BB mice. The exons 2-7 of mouse 4-1bb gene that encode the extracellular domain were replaced by human 4-1BB exons 2-7 in B-hPD-1/hPD-L1/h4-1BBmice.
Protein expression analysis
Strain specific PD-1 expression analysis in homozygous B-hPD-1/hPD-L1/h4-1BB mice by flow cytometry.
Splenocytes were collected from WT and homozygous B-hPD-1/hPD-L1/h4-1BB (H/H) mice stimulated with anti-CD3ε in vivo, and analyzed by flow cytometry with species-specific anti-hPD-1, anti-PD-L1 and anti-4-1BB antibody. Mouse PD-1, PD-L1 and 4-1BB were detectable in WT mice but not in homozygous B-hPD-1/hPD-L1/h4-1BB mice. Human PD-1, PD-L1 and 4-1BB were exclusively detectable in homozygous B-hPD-1/hPD-L1/h4-1BB mice but not WT mice.
Combination therapy of anti-human PD-L1 antibody and anti-human 4-1BB antibody
Antitumor activity of anti-human PD-L1 antibody combined with anti-human 4-1BB antibody in B-hPD-1/hPD-L1/h4-1BB mice.
(A) Anti-human PD-L1 antibody (in house) combined with anti-human 4-1BB antibody (in house) inhibited MC38 tumor growth in B-hPD-1/hPD-L1/h4-1BB mice. Murine colon cancer MC38-hPD-L1 cells were subcutaneously implanted into homozygous B-hPD-1/hPD-L1/h4-1BB mice (female, 6-7 week-old, n=6). Mice were grouped when tumor volume reached approximately 100 mm3, at which time they were treated with human PD-L1 and human 4-1BB antibodies in panel A. (B) Body weight changes during treatment. Values are expressed as mean ± SEM.