Humanized LAG3 Animal Models for Accurate Antibody Screening
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Solution Overview
Problem
Traditional drug development methods for immune-related diseases and cancer therapies face challenges due to the inability of conventional animal models to accurately replicate human tumor microenvironments, leading to high failure rates and discrepancies between animal and clinical trial results.
Innovation Solution
The development of genetically modified animal models that express human or chimeric LAG3 proteins, allowing for more accurate human antibody screening and evaluation, and facilitating drug development by mimicking human immune responses.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional animal models are used for drug screening, then the cost and time for drug development are reduced, but the accuracy and reliability of screening results deteriorate due to species differences and inability to replicate human tumor microenvironment
Solution Approach 1:
The patent creates a copy of the human LAG3 protein expression system in animal models. By introducing human LAG3 gene sequences into animal cells, the model replicates human immune response characteristics without requiring a full human organism, thus improving reliability while maintaining manageable complexity
Solution Approach 2:
The patent applies local quality by selectively humanizing specific components of the animal model - specifically the LAG3 protein expression - rather than attempting to create a completely humanized organism. This targeted approach improves the relevant screening accuracy while avoiding the excessive complexity of full humanization
2Reliability
If in vitro screening approaches are used, then the complexity and cost of drug development are reduced, but the reliability of results deteriorates due to lack of body environment and immune cell interactions
Solution Approach 1:
The patent uses genetically modified animal models as an intermediary system between in vitro screening and clinical trials. These animals express human LAG3 and can be inoculated with human tumor cells, creating a bridge that provides in vivo physiological context while remaining experimentally manageable
Solution Approach 2:
The patent implements a nested structure by placing human tumor cells within animal hosts that express human LAG3 proteins. This creates multiple layers of human biological components nested within an animal system, providing authentic human disease microenvironment while maintaining the simplicity of animal handling
Data Source
AI summary
The present disclosure relates to genetically modified non-human animals that express a human or chimeric (e.g., humanized) LAG3, and methods of use thereof.