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

• Human PD-1 expression under endogenous regulation.
• Preserved immune system development and homeostasis.
• Ideal for immune checkpoint inhibitor (ICI) drug development.
• Enables in vivo antibody validation against human PD-1.
• Applicable in cancer immunotherapy, autoimmune disease models, and chronic infection studies.
• Provides a robust preclinical platform with high translational relevance.

Validation

• Flow cytometry demonstrated exclusive detection of human PD-1 in homozygous PD-1 humanized mice, with no signal in wild-type controls, verifying successful gene humanization
• MC38 tumors implanted in PD-1 humanized mice were significantly inhibited by anti-human PD-1 treatment, validating translational relevance for checkpoint inhibitor studies

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.

Flow cytometry analysis showed human PD-1 expression on activated T cells in homozygous PD-1 humanized mice, confirming replacement of the murine Pdcd1 locus. Both male and female mice (n=6, 8–12 weeks old) were tested. Data demonstrate stable and physiologically relevant expression of human PD-1. This experiment confirms that humanized PD-1 humanized mice express human PDCD1, supporting their application in checkpoint inhibitor studies.

Antitumor activity of anti-human PD-1 antibody in PD-1 humanized mice. (A) Anti-human PD-1 antibody inhibited MC38 tumor growth in PD-1 humanized mice. Murine colon cancer MC38 cells (5×105) were subcutaneously implanted into homozygous PD-1 humanized mice (male, 4-6 weeks 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 as indicated. (B) Body weight changes during treatment. As shown in panel A, anti-human PD-1 antibody was efficacious in controlling tumor growth in PD-1 humanized mice, demonstrating that PD-1 humanized mice provide a powerful preclinical model for in vivo evaluation of anti-human PD-1 antibodies. Values are expressed as mean ± SEM.

Q1: What are PD-1 humanized mice used for?

A1: They are used for preclinical evaluation of anti-human PD-1 antibodies, immuno-oncology research, and autoimmune disease modeling.

Q2: How do PD-1 humanized mice differ from conventional PD-1 knockout mice?

A2: Unlike PD-1 knockouts, PD-1 humanized mice express human PD-1 under its native promoter, allowing in vivo testing of human-specific therapeutics.

Q3: Can PD-1 humanized mice be combined with other humanized models?

A3: Yes, they can be crossed with PD-L1 humanized mice or immune-reconstituted mice for more comprehensive drug testing.

Q4: Are PD-1 humanized mice suitable for autoimmune disease studies?

A4: Yes, they allow investigation of PD-1 pathway dysregulation in autoimmune models such as lupus or arthritis.

Q5: Do PD-1 humanized mice respond to clinically approved checkpoint inhibitors?

A5: Yes, they are validated for anti-PD-1 antibodies like nivolumab and pembrolizumab.