In vivo liver-humanized mouse model
The IMODI partners have investigated a novel in vivo system that provides an optimized platform for increasing our predictivity of patient anti-cancer drug metabolism, potential toxicity, and efficacy.
Through the TK-NOG® liver-humanized model, the IMODI partners are able to predict the patient pharmacological profile of anti-cancer agents. The model can generate a human-specific profile of anti-cancer drug metabolism as well as an efficient microenvironment for metastatic tumor cell homing or for the development of hepatocarcinoma patient-derived-xenograft (PDX) model.
Characteristics of the TK-NOG liver-humanized model:
- Mouse liver is reconstituted with functional human hepatocytes expressing P450 gene.
- Transgenic TK-NOG® mice maintain the transplanted human hepatocytes over 8 months without any chemical adjunction
- Liver-Humanization modifies the PK profile and the metabolism of drugs in mice and predicts hepatotoxicity
- Metabolism profile of drugs in liver-humanized mice is close to Human
- The humanized-liver of TK-NOG® mice is permissive to growth of human tumor cells
The humanized TK-NOG model is a promising preclinical model for:
- Detecting deadly drug side effects by predicting future potential hepatic toxicities in patients,
- Optimizing dose and treatment schedule of anti-cancer agents based on “human” pharmacological profile,
- Evaluating the efficacy of drugs having different in vitro metabolism profile in murine vs human microsomes,
- Evaluating the anti-metastatic activity of drugs,
- Developing PDX models of hepatocarcinoma,
- Studying the role of the tumor microenvironment in liver tumor development and progression as well as the liver metastatic process.
Chi-Mice® is part of a comprehensive portfolio and translational rodent models and services offered by Oncodesign®
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Cette mission s’appuie sur deux activités stratégiques : l’expérimentation de nouveaux traitements anticancéreux et des programmes de découverte de médicaments et biomarqueurs menés en partenariat avec l’industrie pharmaceutique.