C57BL/6-Pdcd1tm1(PDCD1)Bcgen/Bcgen • 110003
PD-1 (Programmed cell death protein 1, PDCD1, CD279) is an inhibitory receptor expressed on activated T cells, B cells, and myeloid cells. By binding to its ligands PD-L1 and PD-L2, PD-1 plays a critical role in immune checkpoint regulation, suppressing T cell activation and maintaining peripheral tolerance. Dysregulated PD-1 signaling contributes to tumor immune evasion and chronic infection.
In PD-1 humanized mice, the murine Pdcd1 gene is replaced with the human PDCD1 gene, ensuring human-specific PD-1 expression under physiological regulation. These mice exhibit normal immune cell development while allowing precise evaluation of anti-human PD-1 therapeutic antibodies in vivo.
PD-1 humanized mice are designed for in vivo PD-1 antibody validation, checkpoint inhibitor development, and preclinical cancer immunotherapy studies. This model bridges translational gaps by expressing human PD-1 under endogenous regulation.
Key Advantages
Validation
Application
PD-1 humanized mice are designed for in vivo PD-1 antibody validation, checkpoint inhibitor development, and preclinical cancer immunotherapy studies. This model bridges translational gaps by expressing human PD-1 under endogenous regulation.
Strain specific analysis of PD-1 gene expression in WT and B-hPD-1 mice by RT-PCR. Mouse PD-1 mRNA was detectable only in splenocytes of wild-type C57BL/6 mice (+/+). Human PD-1 mRNA was detected only in homozygous B-hPD-1 mice, but not in wild-type mice.
Strain specific PD-1 expression analysis in homozygous B-hPD-1 mice by flow cytometry. Splenocytes were collected from wild-type C57BL/6 mice and homozygous B-hPD-1 mice (H/H) stimulated with anti-CD3ε in vivo, and analyzed by flow cytometry with species-specific anti-PD-1 antibody. Mouse PD-1 was detectable in wild-type mice. Human PD-1 was exclusively detectable in homozygous B-hPD-1 mice but not in wild-type mice.
Percentages of human PD-1+ cells in tumor, spleen and blood of B-hPD-1 mice implanted with MC38 cell line. Murine colon cancer MC38 cells (5×105) were subcutaneously implanted into homozygous B-hPD-1 mice (female, 8-9-week-old, n=8).Tumor tissue, splenocytes and blood cells were collected 28 days after implantation. Percentages of human PD-1+ cells in Tregs, CD4+ T cells, CD8+ T cells, B cells, macrophages, dendritic cells and monocytes.
Percentages of human PD-1+ cells in tumor, spleen and blood of B-hPD-1 mice implanted with MC38 cell line. Murine colon cancer MC38 cells (5×105) were subcutaneously implanted into homozygous B-hPD-1 mice (female, 8-9-week-old, n=8).Tumor tissue, splenocytes and blood cells were collected 28 days after implantation. Frequency of human PD-1+ cells in Tregs, CD4+ T cells, CD8+ T cells, B cells, macrophages, dendritic cells and monocytes. Values are expressed as mean ± SEM.
Antitumor activity of anti-human PD-1 antibody in B-hPD-1 mice and C57BL/6 mice. Anti-human PD-1 antibody inhibited MC38 tumor growth in B-hPD-1 mice. (A) Murine colon cancer MC38 cells (5×105) were subcutaneously implanted into homozygous B-hPD-1 mice (female, 6 week-old, n=6). Mice were grouped when tumor volume reached approximately 100 mm3, at which time they were treated with anti-human PD-1 antibody and schedules indicated in panel A. (B) Murine colon cancer MC38 cells (5×105) were subcutaneously implanted into wild-type C57BL/6 mice (female, 6 week-old, n=6). Mice were grouped when tumor volume reached approximately 100 mm3, at which time they were treated with anti-human PD-1 antibody and schedules indicated in panel B. Results showed that human PD-1 antibody X2 was efficacious in controlling tumor growth in the homozygous B-hPD-1 mice but not in the wild-type C57BL/6 mice, demonstrating that B-hPD-1 mice provide a powerful preclinical model for in vivo evaluation of anti-human PD-1 antibodies. Values are expressed as mean ± SEM.
Antitumor activity of anti-human PD-L1 antibody in B-hPD-1 and C57BL/6 mice. Anti-human PD-L1 antibody atezolizumab inhibited MC38-hPD-L1 tumor growth in B-hPD-1 mice (A) and wild type C57BL/6 mice (B). Murine colon cancer MC38-hPD-L1 cells (2×105) were subcutaneously implanted into homozygous B-hPD-1 mice and C57BL/6 mice (female, 6-8 week-old, n=6). Mice were grouped when tumor volume reached approximately 100 mm3, at which time they were treated with anti-human PD-L1 antibody with doses and schedules indicated in panel. Anti-human PD-L1 antibody was efficacious in controlling tumor growth in homozygous B-hPD-1 mice (A) and wild-type C57BL/6 mice (B). Values are expressed as mean ± SEM.
Antitumor activity of anti-human PD-1 antibody in B-hPD-1 mice. (A) Anti-human PD-1 antibody inhibited MC38 tumor growth in B-hPD-1 mice. Murine colon cancer MC38 cells (5×105) were subcutaneously implanted into homozygous B-hPD-1 mice (male, 4-6 week-old, n=5). Mice were grouped when tumor volume reached approximately 100 mm3, at which time they were treated with anti-human PD-1 antibody with doses and schedules indicated in panel (A). (B) Body weight changes during treatment. As shown in panel A, anti-human PD-1 antibody was efficacious in controlling tumor growth in B-hPD-1 mice, demonstrating that B-hPD-1 mice provide a powerful preclinical model for in vivo evaluation of anti-human PD-1 antibodies. Values are expressed as mean ± SEM.
Antitumor activity of anti-human PD-1 antibody in B-hPD-1 mice. (A) Anti-human PD-1 antibody inhibited EL4 tumor growth in B-hPD-1 mice. Murine lymphoma cancer EL4 cells were subcutaneously implanted into homozygous B-hPD-1 mice (n=5). Mice were grouped when tumor volume reached approximately 150±50 mm3, at which time they were treated with three anti-human PD-1 antibodies with doses and schedules indicated in panel. (B) Body weight changes during treatment. As shown in panel A, anti-human PD-1 antibodies were efficacious in controlling tumor growth in B-hPD-1 mice, demonstrating that the B-hPD-1 mice provide a powerful preclinical model for in vivo evaluation of anti-human PD-1 antibodies. Values are expressed as mean ± SEM.
Antitumor activity of anti-human PD-L1 antibody (Atezolizumab) in B-hPD-1 mice. (A) Anti-human PD-L1 antibody inhibited MC38-hPD-L1 tumor growth in B-hPD-1 mice. Murine colon cancer MC38-hPD-L1 cells (5×105) were subcutaneously implanted into homozygous B-hPD-1 mice (n=7). Mice were grouped when tumor volume reached approximately 100 mm3, at which time they were treated with anti-human PD-L1 antibody with doses and schedules indicated in panel A. (B) Body weight changes during treatment. As shown in panel A, anti-human PD-L1 antibody was efficacious in controlling tumor growth in B-hPD-1 mice, demonstrating that the B-hPD-1 mice provide a powerful preclinical model for in vivo evaluation of anti-human PD-L1 antibodies. Values are expressed as mean ± SEM.
Antitumor activity of anti-human PD-1 antibody combined with cisplatin in B-hPD-1 mice. (A) Anti-human PD-1 antibody combined with cisplatin inhibited MC38-hPD-L1 tumor growth in B-hPD-1 mice. Murine colon cancer MC38-hPD-L1 cells (5×105) were subcutaneously implanted into homozygous B-hPD-1 mice (female, 5-8 week-old, n=8). Mice were grouped when tumor volume reached approximately 150±50 mm3, at which time they were treated with anti-human PD-1 antibodies and cisplatin with doses and schedules indicated in panel. (B) Body weight changes during treatment. As shown in panel A, combination of anti-hPD-1 antibody and the chemotherapy drug cisplatin shows more efficaciously inhibitory effects than individual groups, demonstrating that the B-hPD-1 mice provide a powerful preclinical model for in vivo evaluating combination therapy efficacy of anti-human PD-1 antibodies and chemotherapy drugs. Values are expressed as mean ± SEM.
Antitumor activity of anti-human PD-L1 antibody (Atezolizumab) combined with cisplatin in B-hPD-1 mice. (A) Anti-human PD-L1 antibody combined with cisplatin inhibited MC38-hPD-L1 tumor growth in B-hPD-1 mice. Murine colon cancer MC38-hPD-L1 cells (5×105) were subcutaneously implanted into homozygous B-hPD-1 mice (female, 5-8 week-old, n=8). Mice were grouped when tumor volume reached approximately 150±50 mm3, at which time they were treated with anti-human PD-L1 antibody and cisplatin with doses and schedules indicated in panel. (B) Body weight changes during treatment. As shown in panel A, combination of anti-hPD-L1 antibody and the chemotherapy drug cisplatin shows more efficaciously inhibitory effects than individual groups, demonstrating that the B-hPD-1 mice provide a powerful preclinical model for in vivo evaluating combination therapy efficacy of anti-human PD-L1 antibodies and chemotherapy drugs. Values are expressed as mean ± SEM.
