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Rodent Immuno-Safety Models

De-risk drug development with early toxicity screening of immunotherapeutic compounds

In Vivo Models of irAE for Safety and Toxicity Screening of Immunotherapies

Study unique immune-related adverse events (irAEs) associated with immunotherapies, using HuGEMM™ and HuCELL™ human target knock-in models. The platforms feature humanized drug targets within a fully functional murine immune system, providing an ideal method for assessing the complex nature of on-target and off-target toxicities of human-specific immunotherapies.

Efficacy and toxicity of human-specific therapies can be assessed in the same animal, enabling determination of the optimal therapeutic window in the same species and providing quick, cost-effective, and robust data to guide future drug development work.

Benefits of the HuGEMM Platform for Safety and Toxicity Screening

  • Efficiently study the safety of a range of targets for human immunotherapies
  • Enable determination of therapeutic index in the same species by assessing both efficacy and toxicity
  • Improve cost effectiveness with onsite pathology/histopathology services, including IHC, ICC, and IF
  • Rapid study initiation for fast turnaround of robust results - study duration optimized to fit client and project needs

Focused Toxicology Analysis of Immunotherapeutic Agents

  • Immune checkpoint inhibitors
  • Immune checkpoint stimulators
  • Bi-specific antibodies
  • Antibody-drug conjugates (ADCs)

Available Models

 

Currently Available HuGEMM Models for Safety and Toxicity Evaluation

HuGEMM models are immunocompetent chimeric mouse models, engineered to express humanized drug targets (instead of their murine counterparts) such as genes encoding for immune checkpoint proteins.

Single Knock-in Double Knock-in Triple Knock-in
B7H3 TIGIT/PVR CD47/Sirpα/PD-1
BTLA PD-L1/TIM-3 CD47/Sirpα/PD-L1
CCR2 PD-L1/TIGIT PD-1/PD-L1/CD137
CCR8 PD-L1/OX40 PD-1/PD-L1/CTLA4
CD137 PD-L1/LAG3 PD-1/PD-L1/IDO-1
CD27 PD-L1/CTLA4 PD-1/PD-L1/LAG-3
CD28 PD-L1/CD47 PD-1/PD-L1/OX40
CD38 PD-L1/CD40 PD-1/PD-L1/TIGIT
CD39 PD-L1/CD27 PD-1/PD-L1/TIM-3
CD3E PD-L1/CD137 PD-1/TIM-3/TIGIT
CD40 PD-1/Tim3  
CD47 PD-1/TIGIT  
CD73 PD-1/Sirpα  
CTLA4 PD-1/PD-L1  
GITR PD-1/OX40  
IL-1b PD-1/LAG3  
LAG3 PD-1/GITR  
OX40 PD-1/CTLA4  
OX40L PD-1/CD47  
PD-1 PD-1/CD40  
PD-L1 PD-1/CD28  
SIGLEC15 PD-1/CD27  
Sirpα PD-1/CD137  
STING PD-1/BTLA  
TIGIT OX40/CD137  
TIM-3 NKG2A/CD94  
TNFR2 IL2RA/IL2  
VEGFR2 CTLA4/Tim3  
  CTLA4/OX40  
  CTLA4/LAG3  
  CTLA4/CD137  
  CD47/Sirpα  
  CD40/CD137  
  CD27/CD137  


Explore Our Collection

Sample Data

 

Safety and Toxicity Readouts Available

  • Cytokine analysis
  • Liver function tests (ALT, AST)
  • Histopathological evaluation of organ toxicity
  • Immune cell infiltration in target organs by IHC, Flow cytometry
  • Complete blood count (CBC)
  • Clinical observations to identify potential adverse effects related to cytokine storm/CRS

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Fig 1. The tumor growth inhibition of urelumab and chimeric urelumab on murine colon tumor CT26.WT in CD137 HuGEMM model. Tumor growth inhibition (TGI) was calculated as: TGI% = (1-Ti/Vi)*100; Ti as the mean tumor volume of the treatment group on the measurement day; Vi as the mean tumor volume of control group at the measurement day.

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Fig 2. Measurement of liver toxicity based on ALT (alanine aminotransferase) and AST (aspartate aminotransferase) levels in CD137 HuGEMM animals. Fasting serum level of ALT (alanine aminotransferase) and AST (aspartate aminotransferase) were measured 2 and 7 days after final dose. One way ANOVA *, **, and *** refer to p<0.05, p<0.01, and p<0.001, respectively.

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Fig 3. Histological assessment of liver inflammation following urelumab and chimeric urelumab treatment in CD137 HuGEMM in vivo model. H&E staining of liver tissue. Liver inflammation was evaluated on a scale of 0-3: 0 = none; 1 = mild; 2 = moderate; 3 = severe.

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Fig 4. Infiltration of CD45+ immune cells in the liver following urelumab and chimeric urelumab treatment in CD137 HuGEMM in vivo model, as indicated by IHC staining - CD45+ cell density were measured by HALO v3.0.311.363.

 

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