Humanized CD3e Animal Models for Accurate Drug Screening
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Solution Overview
Problem
Conventional drug development methods using in vitro screening and conventional experimental animals fail to accurately replicate human disease states and interactions, leading to high failure rates and increased costs in clinical trials due to the inability to mimic the human body's environment and tumor microenvironment.
Innovation Solution
Development of genetically modified non-human animals expressing human or chimeric CD3e proteins, allowing for the creation of humanized animal models that can be used for drug screening and evaluation, particularly for immune-related diseases and cancer therapy, by replacing endogenous CD3e sequences with human or chimeric CD3e sequences to mimic human CD3e function and interactions.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If conventional experimental animals are used for in vivo pharmacological tests, then the complexity of the animal model is reduced, but the accuracy of reflecting human disease state and interaction at targeting sites deteriorates
Solution Approach 1:
The patent applies the copying principle by replacing the endogenous CD3e gene in animals with the human CD3e gene sequence. This creates a humanized animal model that copies the human immune system component, enabling accurate reflection of human disease states and drug interactions while maintaining the simplicity of animal experimentation.
2Reliability
If in vitro screening approaches are used for drug research and development, then the cost and time of initial screening are reduced, but the reliability of predicting in vivo efficacy deteriorates due to inability to provide body environment
Solution Approach 1:
The patent uses humanized animal models as an intermediary system between in vitro screening and clinical trials. These models provide the physiological body environment (tumor microenvironment, stromal cells, extracellular matrix components, immune cell interactions) that bridges the gap between simplified in vitro systems and complex human clinical settings, thereby improving the reliability of in vivo efficacy prediction.
3Measurement precision
If humanized animal models are developed to accurately reflect human disease state, then the accuracy of drug evaluation is improved, but the complexity of model preparation and genetic modification increases
Solution Approach 1:
The patent employs parameter changes by specifically modifying the CD3e gene sequence parameter in the animal genome. By replacing only this specific genetic parameter with the human sequence while maintaining all other physiological parameters unchanged, the model achieves high accuracy in drug evaluation with controlled complexity in model preparation.
Data Source
AI summary
The present disclosure relates to genetically modified non-human animals that express a human or chimeric (e.g., humanized) CD3e (T-cell surface glycoprotein CD3 epsilon chain), and methods of use thereof.