C57BL/6-Pdcd1tm1(PDCD1)BcgenCd274tm1(CD274)BcgenVegfatm1(VEGFA)Bcgen/Bcgen • 112706
| Product name | B-hPD-1/hPD-L1/hVEGFA mice |
|---|---|
| Catalog number | 112706 |
| Strain name | C57BL/6-Pdcd1tm1(PDCD1)BcgenCd274tm1(CD274)BcgenVegfatm1(VEGFA)Bcgen/Bcgen |
| Strain background | C57BL/6 |
| NCBI gene ID | 5133,29126,7422 (Human) |
| Aliases | CD279, PD-1, PD1, SLEB2, hPD-1, hPD-l, hSLE1; B7-H, B7H1, PD-L1, PDCD1L1, PDCD1LG1, PDL1, hPD-L1; MVCD1, VEGF, VPF |
Strain specific PD-1 and PD-L1 expression analysis in wild-type C57BL/6 and homozygous B-hPD-1/hPD-L1/hVEGFA mice by flow cytometry. Splenocytes were collected from wild-type C57BL/6 mice (+/+) and homozygous B-hPD-1/hPD-L1/hVEGFA mice (H/H; H/H; H/H) after stimulated with or without anti-CD3ε in vivo. Mouse PD-1 and PD-L1 were detectable in wild-type C57BL/6 mice. Human PD-1 and PD-L1 were exclusively detectable in homozygous B-hPD-1/hPD-L1/hVEGFA mice but not in wild-type mice.
Strain specific VEGFA expression analysis in wild-type C57BL/6 mice and homozygous B-hPD-1/hPD-L1/hVEGFA mice by ELISA. Lung homogenates were collected from wild-type C57BL/6 mice (+/+) and homozygous B-hPD-1/hPD-L1/hVEGFA mice (H/H; H/H; H/H). Mouse VEGFA was detectable in wild-type mice. Human VEGFA was exclusively detectable in homozygous B-hPD-1/hPD-L1/hVEGFA mice, but not in wild-type mice.
Frequency of leukocyte subpopulations in spleen by flow cytometry. Splenocytes were isolated from wild-type C57BL/6 mice and homozygous B-hPD-1/hPD-L1/hVEGFA mice (n=3, 10-week-old). A. Flow cytometry analysis of the splenocytes was performed to assess the frequency of leukocyte subpopulations. B. Frequency of T cell subpopulations. Percentages of T cells, B cells, NK cells, dendritic cells, granulocytes, monocytes, macrophages, CD4+ T cells, CD8+ T cells and Tregs in B-hPD-1/hPD-L1/hVEGFA mice were similar to those in C57BL/6 mice, demonstrating that humanization of PD-1, PD-L1 and VEGFA does not change the frequency or distribution of these cell types in spleen. Values are expressed as mean ± SEM. Significance was determined by two-way ANOVA test. *P < 0.05, **P < 0.01, ***p < 0.001.
Antitumor activity of anti-PD-1/VEGFA bispecific antibody (ivonescimab analog, in-house) in B-hPD-1/hPD-L1/hVEGFA mice. (A) Anti-PD-1/VEGFA bispecific antibody inhibited B-hVEGFA MC38 tumor growth in B-hPD-1/hPD-L1/hVEGFA mice. Murine colon cancer B-hVEGFA MC38 cells were subcutaneously implanted into homozygous B-hPD-1/hPD-L1/hVEGFA mice (female, 8-week-old, n=6). Mice were grouped when tumor volume reached approximately 70-90 mm3, at which time they were intraperitoneally injected with anti-PD-1/VEGFA bispecific antibody indicated in panel. (B) Body weight changes during treatment. As shown in panel A, anti-PD-1/VEGFA bispecific antibody was efficacious in controlling tumor growth in B-hPD-1/hPD-L1/hVEGFA mice, demonstrating that the B-hPD-1/hPD-L1/hVEGFA mice provide a powerful preclinical model for in vivo evaluation of anti-PD-1/VEGFA bispecific antibodies. Values are expressed as mean ± SEM. Significance was determined by two-way ANOVA test. *P < 0.05, **P < 0.01, ***P < 0.001.
The overage of this tumor model is 50%.
Antitumor activity of Bevacizumab & Keytruda in B-hPD-1/hPD-L1/hVEGFA mice. Murine colon cancer B-hVEGFA MC38 cells were subcutaneously implanted into homozygous B-hPD-1/hPD-L1/hVEGFA mice (female, 8-week-old, n=6). Mice were grouped when tumor volume reached approximately 70-90 mm3, at which time they were intraperitoneally injected with anti-PD-1 & anti-VEGFA antibody indicated in panel. As shown in panel A, Bevacizumab was efficacious in controlling tumor growth in B-hPD-1/hPD-L1/hVEGFA mice. The combination of these two antibodies is not more effective than monotherapy. Values are expressed as mean ± SEM.
The overage of this tumor model is 40%.
Antitumor activity of Ivonescimab (also known as AK112) in B-hPD-1/hPD-L1/hVEGFA mice. Murine colon cancer B-hVEGFA/hPD-L1 plus MC38 cells were subcutaneously implanted into homozygous B-hPD-1/hPD-L1/hVEGFA mice (male, 8-week-old, n=5). Mice were grouped when tumor volume reached approximately 300 mm3, at which time they were intraperitoneally injected with Ivonescimab indicated in panel. As shown in panel A, Ivonescimab was efficacious in controlling tumor growth in B-hPD-1/hPD-L1/hVEGFA mice. Values are expressed as mean ± SEM.
The overage of this tumor model is 60%.
