Humanized TIM-3 Animal Model for Drug Screening
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Solution Overview
Problem
Traditional drug development for immune-related diseases and cancers using in vitro screening and conventional animal models is inefficient due to the inability to replicate the human body's environment and tumor microenvironment, leading to high failure rates and discrepancies in clinical trial results.
Innovation Solution
Development of a humanized animal model expressing human or chimeric TIM-3 protein, allowing for the study of TIM-3 function and the evaluation of anti-TIM-3 antibodies in a more relevant biological system, including the use of genetically modified mice with humanized TIM-3 and other immunomodulatory genes for drug screening and cancer therapy.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional animal models are used for drug screening, then the complexity of the model is low and ease of operation is high, but the reliability of results for predicting human clinical outcomes deteriorates due to species differences
Solution Approach 1:
The patent applies local quality by selectively humanizing specific genes (TIM-3 and associated genes) in the animal model rather than completely replacing the animal genome. This targeted approach introduces human-specific biological characteristics at the genetic level while maintaining the overall animal model structure, thereby improving reliability for human drug screening without requiring complete model complexity
Solution Approach 2:
The humanized animal model serves as an intermediary system between conventional animal models and human clinical trials. By incorporating human TIM-3 genes and related immunomodulatory genes into the animal genome, the model acts as a bridge that better mimics human biological responses to drugs, improving predictive reliability while avoiding the complexity of direct human testing
2Reliability
If in vitro screening approaches are used for drug development, then the ease of operation is high and cost is low, but the reliability deteriorates due to inability to provide body environment such as tumor microenvironment and immune cell interaction
Solution Approach 1:
The humanized animal model acts as an intermediary system that bridges the gap between simple in vitro screening and complex human clinical trials. The model incorporates human TIM-3 genes and maintains intact tumor microenvironments with immune cell interactions, providing a biologically relevant system that improves drug evaluation reliability while avoiding the excessive complexity and cost of human trials
Solution Approach 2:
The patent changes the biological parameters of the animal model by introducing human TIM-3 genes and associated human immunomodulatory genes. This genetic parameter modification enables the model to better reflect human physiological conditions, including tumor microenvironment characteristics and immune cell interactions, thereby improving the reliability of drug screening results
3Reliability
If completely humanized animal models are developed to improve clinical trial prediction, then the reliability of results improves, but the difficulty of manufacture and cost increase significantly
Solution Approach 1:
The patent implements local quality by selectively humanizing only the necessary genes (TIM-3 and selected immunomodulatory genes) rather than completely replacing the animal genome with human genes. This targeted gene introduction approach achieves sufficient reliability for clinical trial prediction while significantly reducing the technical difficulty and cost compared to complete humanization
Solution Approach 2:
The patent applies partial action by introducing a limited set of human genes (TIM-3 and associated genes) rather than implementing complete humanization. This partial humanization strategy provides adequate predictive reliability for drug development while avoiding the excessive complexity, time, and cost associated with comprehensive genome replacement
Data Source
AI summary
The present disclosure relates to the genetically modified non-human animals that express a human or chimeric (e.g., humanized) T-cell immunoglobulin and mucin-domain containing-3 (TIM-3), and methods of use thereof.