Basic Information

Strain Name
C57BL/6-Pdcd1tm1(PDCD1) Cd274tm1(CD274)Lag3tm3(LAG3)/Bcgen
Common Name
B-hPD-1/hPD-L1/hLAG3 plus mice
Background
C57BL/6
Catalog Number
130572
Related Genes
PD-1 (Programmed death-1) ;CD274 (CD274 antigen); LAG3 (lymphocyte-activation gene 3)

Targeting strategy

Gene targeting strategy for B-hPD-1/hPD-L1/hLAG3 mice. The exon 2 of mouse Pd-1 gene that encodes the extracellular domain was replaced by human PD-1 exon 2 in B-hPD-1/hPD-L1/hLAG3 mice. The exon 3 of mouse Pd-l1 gene that encodes the extracellular domain was replaced by human PD-L1 exon 3 in B-hPD-1/hPD-L1/hLAG3 mice. The exons 2-7 of mouse Lag3 gene that encode the extracellular domain were replaced by human LAG3 exons 2-7 in B-hPD-1/hPD-L1/hLAG3 mice.

Details

Protein expression analysis

Strain specific PD-1, PD-L1 and LAG3 expression analysis in homozygous B-hPD-1/hPD-L1/LAG3(plus) mice by flow cytometry. Splenocytes were collected from WT and homozygous B-hPD-1/hPD-L1/hLAG3 (H/H) mice, and analyzed by flow cytometry with species-specific anti-PD-1, anti-PD-L1 and anti-LAG3 antibody. Mouse PD-1, PD-L1 and LAG3 were detectable in WT mice. Human PD-1, PD-L1 and LAG3 were exclusively detectable in homozygous B-hPD-1/hPD-L1/hLAG3 but not WT mice.

Strain specific PD-1, PD-L1 and LAG3 expression analysis in homozygous B-hPD-1/hPD-L1/LAG3(plus) mice by flow cytometry. Splenocytes were collected from WT and homozygous B-hPD-1/hPD-L1/hLAG3 (H/H) mice stimulated with anti-CD3ε in vivo, and analyzed by flow cytometry with species-specific anti-PD-1, anti-PD-L1 and anti-LAG3 antibody. Mouse PD-1, PD-L1 and LAG3 were detectable in WT mice. Human PD-1, PD-L1 and LAG3 were exclusively detectable in homozygous B-hPD-1/hPD-L1/hLAG3 but not WT mice.

 

Combination therapy of pembrolizumab and anti-human LAG3 antibodies

Antitumor activity of pembrolizumab and anti-human LAG3 antibodies in B-hPD-1/hPD-L1/hLAG3(plus) mice. (A) human PD-1 antibody combined with anti-human LAG3 antibody inhibited MC38 tumor growth in B-hPD-1/hPD-L1/hLAG3(plus) mice. Murine colon cancer hPD-L1 MC38 cells were subcutaneously implanted into homozygous B-hPD-1/hPD-L1/hLAG3(plus) mice (female, 7-8 week-old, n=5). Mice were grouped when tumor volume reached approximately 100 mm3, at which time they were treated with pembrolizumab, relatlimab, LBL-007 and IBI110 with doses and schedules indicated in panel A. (B) Body weight changes during treatment. As shown in panel A, combination of pembrolizumab and relatlimab/LBL-007/IBI110 shows more inhibitory effects than individual groups, demonstrating that the B-hPD-1/hPD-L1/hLAG3(plus) mice provide a powerful preclinical model for in vivo evaluating combination therapy efficacy of hPD-1 antibodies and hLAG3 antibodies. Values are expressed as mean ± SEM.

 

Combination therapy of pembrolizumab and relatlimab

Antitumor activity of pembrolizumab and relatlimab in B-hPD-1/hPD-L1/hLAG3(plus) mice. (A) human PD-1 antibody combined with anti-human LAG3 antibody inhibited MC38 tumor growth in B-hPD-1/hPD-L1/hLAG3(plus) mice. Murine colon cancer hPD-L1 MC38 cells were subcutaneously implanted into homozygous B-hPD-1/hPD-L1/hLAG3(plus) mice (female, 7-8 week-old, n=5). Mice were grouped when tumor volume reached approximately 100 mm3, at which time they were treated with pembrolizumab and relatlimab with doses and schedules indicated in panel A. (B) Body weight changes during treatment. As shown in panel A, combination of pembrolizumab and relatlimab shows more inhibitory effects than individual groups, demonstrating that the B-hPD-1/hPD-L1/hLAG3(plus) mice provide a powerful preclinical model for in vivo evaluating combination therapy efficacy of hPD-1 antibodies and hLAG3 antibodies. Values are expressed as mean ± SEM.

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