Humanized Mouse Models for In vivo Immunotherapy Evaluation

PBMC, CD34+, and GEM Models

At TD2, we specialize in providing comprehensive in vivo studies for the evaluation of immunotherapies using advanced humanized mouse models. Our portfolio includes PBMCs, CD34+, and humanized immune checkpoint inhibitor GEM models, offering robust platforms to assess the efficacy and safety of novel immuno-oncology drugs. These models closely mimic human immune responses, enabling precise preclinical evaluations and accelerating the development of effective immunotherapy treatments. Additionally, our on-site flow cytometry capabilities ensure the accurate engraftment of human immune cells.

Features and Benefits:

  • Accurate Human Immune Response Simulation: Our humanized mouse models, including PBMC, CD34+, and humanized immune checkpoint GEM models, closely replicate human immune system interactions, providing reliable insights into therapy efficacy.

  • Enhanced Predictability: These models offer superior predictive power for clinical outcomes, bridging the gap between preclinical studies and human clinical trials.

  • Diverse Immune Contexts: With a range of models available, we can tailor studies to various immune contexts, ensuring comprehensive evaluation of immune-oncology drugs.

  • Accelerated Drug Development: Utilizing these advanced models accelerates the drug development process by providing early and accurate data on therapeutic potential and safety.

  • Customized Study Design: TD2 offers bespoke study designs to meet specific research needs, leveraging our expertise and advanced models to optimize preclinical evaluations.

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PBMC Humanized Mouse Models


Benefits of using PBMC mice for I/O research

  • Human Immune Cell Integration: PBMC models incorporate human peripheral blood mononuclear cells, allowing researchers to study interactions between human immune cells and cancer cells in a controlled in vivo environment, leading to more relevant preclinical data.

  • Immune Checkpoint Inhibition Evaluation: These models are ideal for evaluating the efficacy of immune checkpoint inhibitors and other immunotherapies, providing critical insights into their mechanisms of action and potential clinical efficacy.

Fig 1. Effect of Hu-PBMCs Alone and in Combination with Anti-hPD-1 on Body Weight
in the Subcutaneous MKN45 Human Gastric Tumor Xenograft Model
(N=5 mice/group)

Fig 2. Effect of Hu-PBMCs Alone and in Combination with Anti-hPD-1 on Tumor Volume
in the Subcutaneous MKN45 Human Gastric Tumor Xenograft Model
(N=5 mice/group)


CD34+ Humanized Mouse Models


Benefits of using CD34+ mice for I/O research

  • Long-Term Human Immune System Development: CD34+ mouse models are engrafted with human hematopoietic stem cells, leading to the development of a long-term, self-renewing human immune system. This allows for extended studies on immune response and therapy effects over time.

  • Multifaceted Immuno-Oncology Research: These models support the study of a wide range of immuno-oncology treatments, including cell therapies, vaccines, and antibody-based therapies, providing a versatile platform for preclinical research.

  • High Relevance to Human Hematopoiesis: CD34+ models closely mimic human hematopoiesis and immune cell differentiation, making them highly relevant for studying hematologic malignancies and evaluating hematopoietic toxicities of new immunotherapies.

Fig 3. The Subcutaneous HT1376 Human Bladder Tumor Xenograft Model in
CD34+ and Naive NCG Mice - % Body Weight Change
(N=5 mice/group)

Fig 4. The Subcutaneous HT1376 Human Bladder Tumor Xenograft Model in
CD34+ and Naive NCG Mice - Tumor Growth Curve
(N=5 mice/group)


GEM Humanized Immune Checkpoint Inhibitor Models

humanized-mouse-models-1


Benefits of using humanized immune checkpoint inhibitors for I/O research

  • Enable the evaluation of human-specific biological therapies in vivo faster than traditional animal models
  • Double KI models allow combination therapy evaluation
  • Lack of expression of the murine target gene, avoiding cross-reactivity
  • Provides a more predictive model for how drugs will perform in the clinic



Fig 5. Humanized PD-1 mice (hPD-1) were inoculated
with MC-38 cells expressing human PD-L1 (hPD-L1).
Mice were treated with Nivolumab (10 mg /kg) OD 3 x 4
Results are shown as TV + /- SEM


Fig 6. Individual spider plots of humanized PD1 mice (hD1) inoculated
with MC-38 cells expressing human PD-L1 (hPD-L1)
Mice were treated with vehicle (left) or Nivolumab (10 mg/kg) QD 3 x 4 (right)


Available Humanized Immune Checkpoint Inhibitor Models

Single Target Double Target Triple Target
hACE2 hTREM2 hCD47/hSIRPα hFcgRs/hCD47/hSIRPα
hCD3E hCD22 hPD1/hLAG3 hPD1/hPDL1/hCD137
hHRAS hCTLA4 hPD1/hBTLA hPD1/hPDL1/hCD40
hPD1 hLAG3 hPD1/hOX40 hPD1/hPDL1/hCD73
hTIM3 hSIRPα hPD1/hCD137 hPD1/hPDL1/hLAG3
hBTLA hVISTA hPD1/hPDL1 hPD1/hPDL1/hOX40
hCD3EDG hCD27 hPD1/hCD47 hPD1/hPDL1/hSIRPα
hIFNAR1 hDPP4 hPD1/hSIRPα hPD1/hPDL1/hTIGIT
hPDL1 hLLRC32 hPD1/hCSF1R hPD1/hPDL1/hTIM3
hTMPRSS2 hSTING1 hPD1/hTIGIT hPD1/hPDL1hCTLA4
hCCN1 hVTCN1 hPD1/hCTLA4  
hCD47 hCD28 hPD1/hTIM3  
hIL12RB1 hFcgRs hPD1/hGITR  
hPVRIG hOX40 hPDL1/hB7H3  
hTNFR2 hTIGIT    
hCD137 hCD38    
hCD73 hFcRn    
hIL12RB2 hRANK    
hSIGLEC15      

Humanized PDX Evaluation for Immuno-oncology

Conducting oncology research using Patient-Derived Xenograft (PDX) models with humanized mice offers a highly translational platform for assessing new cancer therapies. This approach combines the relevance of human tumor biology with an immune system that closely mimics human responses, enhancing the predictive power of preclinical studies. By leveraging humanized PDX models, researchers can gain valuable insights into the efficacy and mechanism of action of novel treatments in a setting that closely resembles the clinical scenario.

  • Enhanced Predictive Value: Humanized PDX models provide a more accurate prediction of how human tumors will respond to new therapies.
  • Immune System Relevance: These models incorporate a human immune system, allowing for the assessment of immuno-oncology therapies and their interactions with the tumor microenvironment.
  • Personalized Medicine Insights: PDX models derived from individual patients' tumors can be used to study personalized treatment approaches, leading to more targeted and effective therapeutic strategies.

Models Available:

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Immuno-Oncology

Immuno-oncology

Comprehensive preclinical services for immuno-oncology.

TD2’s extensive knowledge of CAR-T in both solid and hematologic tumors enables rapid evaluation of your CAR-T cell therapy, moving your therapeutic program forward to the clinic.

Large panel of human and murine tumor models

Cell therapy models


  • 8 years of experience in cell therapy
  • Expertise includes: CAR-T, NK-CAR, IPS-NKs, Macrophages

Syngeneic mouse models


  • Fully characterized for gene expression, TIL baseline populations, and response to common immune checkpoint inhibitors

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TD2 navigates the complexities of drug discovery to guide you down a smarter path for earlier, more complete results.

Contact us today to learn more about our humanized mouse studies and how we can set your treatment up for success from the start.