PD1 Humanized Mouse Models
PD1 humanized mice enable preclinical testing of anti human PD1 therapeutic antibodies including pembrolizumab and nivolumab in immunocompetent mouse systems.
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Why Humanize PD1
Species Specificity of Therapeutic Antibodies
Anti PD1 therapeutic antibodies are engineered specifically for human PD1:
- Antibody epitopes designed against human PD1 sequence
- Limited or no binding to mouse PD1 ortholog
- Cannot evaluate efficacy in wildtype mice
- Surrogate antibodies against mouse PD1 may not predict human responses
Humanized PD1 mice express the human target, enabling direct testing of clinical antibody candidates.
Maintaining Immunocompetent System
PD1 humanization preserves the mouse immune system:
- Functional T cells expressing human PD1
- Intact tumor microenvironment interactions
- Normal immune cell development and function
- Physiological PD1/PDL1 axis signaling
Unlike xenograft models in immunodeficient mice, humanized checkpoint models enable immunotherapy studies in animals with functional adaptive immunity.
Translational Relevance
Humanized models improve translation to clinical outcomes:
- Test the actual clinical candidate, not a surrogate
- Evaluate on target effects with human protein engagement
- Develop and validate human specific biomarkers
- Support regulatory submissions with relevant efficacy data
Humanization Strategies
Extracellular Domain Humanization
The most common approach replaces the mouse PD1 extracellular domain with human sequence while retaining mouse intracellular signaling domains:
This strategy is optimal for therapeutic antibody testing where the goal is to evaluate antibody binding and blocking activity.
Complete Gene Humanization
Full replacement of mouse Pdcd1 with human PDCD1:
Conditional Humanization
Conditional approaches enable controlled humanization:
Applications
Anti PD1 Antibody Efficacy Testing
Primary application for PD1 humanized mice:
- Test pembrolizumab, nivolumab, and other clinical antibodies
- Evaluate novel anti PD1 candidates
- Compare antibody potency and characteristics
- Assess Fc effector function contributions
Combination Immunotherapy
PD1 humanized mice support combination studies:
- Anti PD1 plus chemotherapy
- Anti PD1 plus radiation
- Anti PD1 plus targeted therapy
- Anti PD1 plus other checkpoint inhibitors (dual humanized models)
Tumor Model Compatibility
PD1 humanized mice on C57BL/6 background are compatible with syngeneic tumor models. BALB/c background humanized models enable use of CT26, 4T1, and other BALB/c compatible tumor lines.
Biomarker Development
Humanized models support translational biomarker work:
- Human PD1 detection with clinical grade antibodies
- Pharmacodynamic biomarker validation
- Receptor occupancy assessment
- Immune activation markers
Tumor Model Compatibility
Combination with Other Humanized Checkpoints
PD1 humanization can be combined with other checkpoint humanizations. Dual humanized models enable evaluation of combination checkpoint inhibitor regimens using clinical antibodies against both targets.
Combination Models
For complex combination studies, multiple checkpoint humanizations can be combined through breeding or sequential targeting. Our scientific team advises on efficient strategies for generating multi humanized models.
Technical Considerations
Strain Background
Choose strain background based on tumor model compatibility:
- C57BL/6: Compatible with MC38, B16, LLC, E0771
- BALB/c: Compatible with CT26, 4T1, EMT6
Our scientific team advises on optimal strain background for your research program.
Functional Validation
Validate humanized PD1 function in your experimental system:
- Confirm human PD1 surface expression on T cells
- Verify therapeutic antibody binding
- Test functional checkpoint blockade
- Compare to wildtype controls
Selected Publications
Humanized checkpoint models generated by ingenious targeting laboratory have supported immuno oncology research:
Mlynarczyk C et al. 2023. BTG1 mutation yields supercompetitive B cells primed for malignant transformation. Science 379(6629): eabj0412.
Chakrabarti S et al. 2024. Touch sensation requires the mechanically gated ion channel ELKIN1. Science 383(6686): 992 to 998.
Clausen BE et al. 1999. Conditional gene targeting in macrophages and granulocytes using LysMcre mice. Transgenic Research 8(4): 265 to 277.
What Researchers Say
“iTL produced a new conditional mouse model for us and the quality of service was exceptional. The team is extremely knowledgeable and the work was completed at the highest possible standards. My project manager was excellent and always happy to answer technical questions and keep me up to date with progress and potential problems. I would recommend iTL highly and will use them again in the future if I need to generate a new mouse line.”
— Albert Basson, PhD
King's College London
Start Your PD1 Humanization Project
Our scientific consultants are ready to discuss your PD1 humanization requirements and recommend the optimal strategy for your immuno oncology program. Initial consultation is provided at no charge and includes humanization approach recommendations, strain background guidance, and timeline estimates.
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