Humanized Syngeneic Models
Humanized mouse models enable rapid testing of human target-specific immunotherapy drug candidates by providing genetically engineered human targets in a fully immunocompetent host.
Our humanized mouse models can help you understand your drug's mechanisms of action, kinetics, toxicity profile, and potency, allowing you to select a drug candidate with the highest chance of success in the clinic.
Our team of experts have extensive knowledge in the field of preclinical modelling and long-standing expertise in assessing the efficacy and potency of immuno-oncology drug candidates using humanized mouse models.
What we offer:
- A panel of well-established models expressing clinically-relevant human targets (developed in collaboration with genOway)
- Models suitable for response to human immune checkpoint inhibitors (e.g. Pembrolizumab, Nivolumab, Ipilimumab) to evaluate combinations strategies with your test compound
- Flow cytometry readout for immune cell profiling
- A team of expert immunologist available to guide your study design and support data analysis
Reach out today to discuss how we can fast-track your immunotherapy research.
Humanized Syngeneic Mouse Models Available at Reaction Biology
Setup:
The humanized hPD-1 mouse has been developed in the mouse C57BL/6N background. To this mouse strain’s PD-1 locus, a chimeric PD-1 with a human extracellular domain, a murine transmembrane domain, and an intracellular domain has been inserted (C57BL/6N-Pdcd1tm1.1((PDCD1)Geno)), allowing human-specific therapeutic Abs to interact with the human domain of this chimeric PD-1 protein, while the murine intracellular domain facilitates all murine specific downstream events.
Goal:
For in vivo efficacy and potency assessment and profiling of human immune checkpoint hPD-1 targeting immunotherapeutic agents in a fully immune-competent humanized mouse model.
Tumor cell line:
MC38-CEA, expressing human CEA, was engrafted subQperior™ in the hPD-1 expressing C57BL/6N model, to test the efficacy of human specific immunotherapeutic agent Pembrolizumab targeting human immune checkpoint hPD-1. As a control murine-specific anti-PD-1 Abs (RPM1-14) was used to allow for monitoring of human-specific anti-tumor response.
Results: 
In vivo anti-tumor activity in a MC38-CEA subQperiorTM tumor model in hPD-1 expressing mice.
Whereas anti-murine PD-1 treatment shows no activity, anti-human PD-1 treatment delays MC38-CEA tumor cell growth.
ELISpot analysis reveals a higher number of IFN-γ+ secreting cells in hPD-1 C57/BL6 mice treated with Prembrolizumab.
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