Humanized LAG-3 Animal Models for Accurate Immune Therapy Screening
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Traditional drug development methods for inhibitory receptors, such as those targeting the immune system, face challenges due to the inability of in vitro screening to replicate the body's environment and the differences between human and animal test results, leading to high failure rates and inefficiencies in drug development.
Innovation Solution
The development of genetically modified animal models that express humanized Lymphocyte Activation Gene 3 (LAG-3) proteins, allowing for more accurate in vivo testing and evaluation of anti-LAG-3 antibodies and therapies.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If in vitro screening approaches are used for traditional drug development, then the screening process is simple and fast, but the results cannot reflect the real body environment and have high failure rates
Solution Approach 1:
The patent introduces humanized animal models as an intermediary system between in vitro screening and clinical trials. These models express human LAG-3 proteins in their bodies, allowing drug candidates to be tested in a living organism that more closely mimics human physiology while still being experimentally controllable. This intermediary step bridges the gap between simplified cell culture and complex human clinical environments.
2Reliability
If conventional experimental animals are used for in vivo pharmacological tests, then the tests can be conducted in living organisms, but the results do not reflect the real human disease state due to species differences
Solution Approach 1:
The patent applies local quality by introducing human LAG-3 proteins specifically into certain cells or tissues of the animal model, rather than requiring complete humanization of the entire organism. This allows the model to have human-like characteristics at the specific molecular target site while maintaining the simplicity and controllability of the animal system for other physiological functions.
3Reliability
If humanized animal models are developed to improve drug screening accuracy, then the test results better reflect human disease states, but the model development becomes more complex and time-consuming
Solution Approach 1:
The patent implements partial humanization by introducing only the specific human LAG-3 protein genes into the animal model, rather than attempting to humanize the entire genome. This partial action approach achieves the necessary reliability for LAG-3 targeted drug screening while avoiding the excessive time and complexity of complete humanization, allowing the model to be developed more efficiently for the specific research purpose.
Data Source
AI summary
The present disclosure relates to the genetically modified non-human animals that express a human or chimeric (e.g., humanized) Lymphocyte Activation Gene 3 (LAG-3), and methods of use thereof.