Epithelial Stem Cell Cancer Models for Immune Interaction
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Solution Overview
Problem
Current cancer-bearing animal models, such as xenograft and genetically modified mouse models, face challenges in reproducing human cancer interactions and immune system responses, and are difficult to produce with various gene mutations, limiting their effectiveness in evaluating therapeutic agents for lung cancer.
Innovation Solution
Development of a method using epithelial tissue stem cells derived from adults, specifically bronchioalveolar stem cells lacking tumor suppressor genes, which are 3D cultured and transplanted into non-human animals with a normal immune system to create cancer-bearing models with specific gene mutations, allowing for the evaluation of anticancer agents and immune agonists.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If xenograft mouse models are used to transplant human cancer cells into immunodeficient mice, then cancer cell transplantation is achieved, but the interaction between cancer cells and immune system cannot be completely reproduced
Solution Approach 1:
The patent uses allograft mouse models that copy the human cancer cell characteristics while maintaining the mouse immune system's functionality. Instead of using human cancer cells in immunodeficient mice (xenograft), the invention employs mouse cancer cells with humanized genetic modifications that can be transplanted into syngeneic mice with normal immune systems, thereby copying the essential cancer characteristics while preserving immune interaction capability
Solution Approach 2:
The patent changes the key parameter of immune system status from immunodeficient to normal/functional. By using syngeneic mice with intact immune systems instead of immunodeficient mice, the model allows for comprehensive study of cancer-immune interactions while maintaining the ability to reproduce human cancer characteristics through genetic modifications
2Manufacturing precision
If genetically modified mouse models are used to produce cancer-bearing models with specific gene mutations, then models with specific mutations can be created, but a long period of time is required for production
Solution Approach 1:
The patent applies preliminary action by pre-establishing cell lines with specific gene mutations (such as KRAS, EGFR, ALK mutations) that can be directly transplanted into mice. Instead of generating each cancer model from scratch through lengthy genetic modification processes, the invention uses pre-characterized cell lines with known mutations, significantly reducing production time while maintaining genetic precision
Solution Approach 2:
The patent copies human cancer cell genetic characteristics into mouse cell models. By creating mouse cancer cell lines that replicate specific human cancer gene mutations and characteristics, the invention enables rapid model generation that mirrors human disease states without requiring de novo genetic engineering for each model
3Adaptability or versatility
If allograft mouse models are used to transplant mouse cancer cells into syngeneic mice with normal immune system, then immune system interaction can be studied, but there are very few cancer cell lines derived from mouse
Solution Approach 1:
The patent creates a universal platform using syngeneic mouse models with normal immune systems that can evaluate multiple types of cancer cell lines with different genetic mutations. This single model system serves multiple functions: studying immune interactions, testing various gene mutations (KRAS, EGFR, ALK, ROS1), and evaluating therapeutic agents, thereby compensating for the limited availability of specific mouse cancer cell lines
Solution Approach 2:
The patent changes the availability parameter by generating diverse cancer cell lines with specific gene mutations that can be used in the allograft model. By creating cell lines with human-relevant mutations (KRAS G12D, EGFR L858R, ALK EML4-ALK fusion, ROS1 fusion) in mouse cells, the invention expands the variety of usable cell lines while maintaining compatibility with the syngeneic immune system
Data Source
AI summary
Provided is an epithelial tissue stem cell derived from an adult, which lacks at least one tumor suppressor gene.