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Catalog Models

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:

Human extracellular domain provides antibody binding epitopes
Mouse transmembrane and intracellular domains preserved
Normal downstream signaling maintained
Compatibility with mouse immune system

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:

Complete human PDL1 protein sequence
Human specific expression characteristics
Study human PDL1 biology comprehensively
Appropriate for mechanistic studies beyond antibody testing

Considerations for PDL1 Humanization

PDL1 humanization has specific considerations:

PDL1 expressed on host immune cells and tumor cells
Syngeneic tumors continue to express mouse PDL1
For complete humanization of tumor PDL1, consider human PDL1 expressing tumor cell lines
Host humanization sufficient for many applications

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

Tumor ModelTumor TypePDL1 Expression
MC38Colon carcinomaModerate to high
B16MelanomaVariable
LLCLung carcinomaVariable
E0771Breast carcinomaModerate

PDL1 vs PD1 Humanization

FactorPDL1 HumanizationPD1 Humanization
TargetLigand on tumor/APCReceptor on T cells
ExpressionTumor, DC, macrophagesActivated T cells
Antibody targetsAtezolizumab, durvalumabPembrolizumab, nivolumab
MechanismBlock ligandBlock receptor

Dual PD1/PDL1 Humanization

For comprehensive PD1/PDL1 axis studies, both targets can be humanized:

Complete humanization of checkpoint axis
Test PD1 and PDL1 antibodies in same model
Mechanistic studies of pathway biology
Combination PD1 + PDL1 blocking approaches

Combination Models

CombinationApplications
PDL1 + PD1Complete PD1/PDL1 axis humanization
PDL1 + CTLA4Dual checkpoint combinations
PDL1 + LAG3Novel combination strategies
PDL1 + TIGITEmerging checkpoint combinations

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

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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.

Frequently Asked Questions

Full humanization replaces the entire mouse PDL1 gene with human PDL1 sequence. ECD-only humanization replaces only the extracellular domain while retaining mouse transmembrane and cytoplasmic domains. Full humanization is preferred for antibody testing; ECD-only may preserve some mouse signaling functions.

Yes. PDL1 humanization can be combined with PD1, CTLA4, LAG3, TIM3, or other checkpoint humanizations to create double, triple, or multi-checkpoint models. PD1+PDL1 dual humanization enables comprehensive study of the checkpoint axis.

Pre-germline characterization includes Southern blot analysis to confirm correct targeting and sequence verification to ensure human sequence fidelity. Post-germline validation includes flow cytometry for surface expression on tumor cells, dendritic cells, and macrophages, Western blot for protein expression, and functional confirmation through binding of anti-PDL1 antibodies (atezolizumab, durvalumab).

Custom humanized model generation includes targeting construct design, ES cell targeting, chimera generation, and germline transmission. Pre-germline characterization enables early validation of targeting and human sequence confirmation before mouse generation. Contact us for current timeline estimates.

PDL1 humanized mice on C57BL/6 background work with syngeneic tumor models (MC38, B16, LLC, E0771). Note that syngeneic tumors express mouse PDL1, but host PDL1 humanization enables testing of antibody effects on host immune and stromal cell PDL1, which is often the predominant effect in checkpoint blockade.