PDL1 Humanized Mouse Models
PDL1 humanized mice enable preclinical testing of anti human PDL1 therapeutic antibodies including atezolizumab, durvalumab, and avelumab in immunocompetent mouse systems.
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Why Humanize PDL1
Species Specificity of Therapeutic Antibodies
Anti PDL1 therapeutic antibodies are engineered specifically for human PDL1:
- Antibody epitopes designed against human CD274 sequence
- Limited cross reactivity with mouse PDL1
- Cannot evaluate efficacy in wildtype mice
- Humanized models enable testing of clinical candidates
PDL1 humanization provides the human target necessary for evaluating anti PDL1 therapeutics.
PDL1 Expression Biology
PDL1 is expressed on multiple cell types relevant to tumor immunity:
- Tumor cells: Direct expression for immune evasion
- Dendritic cells: Regulation of T cell priming
- Macrophages: Tumor associated macrophage function
- Other immune cells: Broad immune regulation
Humanized PDL1 in all expressing cell types enables comprehensive evaluation of anti PDL1 effects across the tumor microenvironment.
Translational Relevance
Humanized models improve translation to clinical outcomes:
- Test the actual clinical candidate
- Evaluate on target effects with human protein engagement
- Assess PDL1 expression and blocking in tumor tissue
- Support biomarker development with human specific reagents
Humanization Strategies
Extracellular Domain Humanization
Replace the mouse PDL1 extracellular domain with human sequence:
Extracellular domain humanization is optimal for therapeutic antibody testing where antibody binding to the surface exposed protein is the primary consideration.
Complete Gene Humanization
Full replacement of mouse Cd274 with human CD274:
Considerations for PDL1 Humanization
PDL1 humanization has specific considerations:
Applications
Anti PDL1 Antibody Efficacy Testing
Primary application for PDL1 humanized mice:
- Test atezolizumab, durvalumab, avelumab, and other clinical antibodies
- Evaluate novel anti PDL1 candidates
- Compare antibody characteristics and potency
- Assess ADCC and other Fc effector contributions
Combination Immunotherapy
PDL1 humanized mice support combination studies:
- Anti PDL1 plus chemotherapy
- Anti PDL1 plus targeted therapy
- Anti PDL1 plus radiation
- Anti PDL1 plus anti PD1 (dual humanized models for mechanistic studies)
Tumor Model Compatibility
PDL1 humanized mice on C57BL/6 background work with common syngeneic models. Note that syngeneic tumors express mouse PDL1. Host PDL1 humanization enables testing of antibody effects on host immune and stromal cell PDL1, which is often the predominant effect in checkpoint blockade.
PDL1 as Biomarker
Humanized models support PDL1 biomarker studies:
- Test clinical grade anti human PDL1 diagnostic antibodies
- Evaluate PDL1 expression scoring in humanized tissues
- Develop companion diagnostic approaches
- Correlate PDL1 expression with response
Tumor Model Compatibility
PDL1 vs PD1 Humanization
Dual PD1/PDL1 Humanization
For comprehensive PD1/PDL1 axis studies, both targets can be humanized:
Combination Models
Multi humanized models enable comprehensive evaluation of combination checkpoint blockade using clinical antibodies.
Technical Considerations
Strain Background
Choose strain background based on experimental requirements:
- C57BL/6: Compatible with MC38, B16, LLC, E0771
- BALB/c: Compatible with CT26, 4T1, EMT6
Functional Validation
Validate humanized PDL1 function in your experimental system:
- Confirm human PDL1 surface expression
- Verify therapeutic antibody binding
- Test functional checkpoint blockade
- Assess PDL1 expression on relevant cell types
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 PDL1 Humanization Project
Our scientific consultants are ready to discuss your PDL1 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.