Intact Tumor Tissue Evaluation with Immune Microenvironment Preservation
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Solution Overview
Problem
Existing cell culture models, including cancer cell lines and animal models, fail to accurately predict the efficacy of cytotoxic and targeted therapies in patients due to the lack of complexity in recapitulating the tumor microenvironment, particularly the presence of immune and stromal cells.
Innovation Solution
A method for long-term evaluation of candidate molecules on intact tumor tissue samples, cultured under conditions that maintain the tumor microenvironment, including immune cells, to assess therapeutic responses.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of operation
If simple cell culture models (cancer cell lines) are used, then ease of operation and cost are improved, but measurement precision and reliability of therapeutic efficacy prediction deteriorate
Solution Approach 1:
The patent creates a copied version of the in vivo tumor microenvironment through organoid cultures derived from patient tumor cells. These organoids replicate the complex cellular architecture, stromal components, and immune cell interactions of actual tumors, providing a more accurate predictive model while remaining cultivable in laboratory settings. This copying approach bridges the gap between simple cell lines and complex animal models.
Solution Approach 2:
The organoid cultures comprise composite structures containing multiple cell types (cancer cells, stromal cells, immune cells) organized in a three-dimensional architecture that mimics the tumor microenvironment. This composite cellular organization preserves the functional interactions between different cell populations, enabling more accurate therapeutic response predictions compared to monoculture cell lines.
2Measurement precision
If complex models (animal models) are used, then measurement precision and reliability are improved, but device complexity, cost, and time requirements worsen
Solution Approach 1:
The patent extracts the essential functional components of the tumor microenvironment (cancer cells, stromal cells, immune cells, extracellular matrix) and reconstructs them in a simplified organoid culture system. This extraction eliminates the need for complex animal models while preserving the critical cell-cell and cell-matrix interactions necessary for accurate therapeutic response prediction.
Solution Approach 2:
Instead of using entire animal models, the patent creates in vitro copies of the relevant tumor microenvironment components. These organoid copies capture the essential biological responses to therapies without requiring the complexity of living animal systems, thereby reducing time, cost, and ethical considerations while maintaining predictive accuracy.
3Measurement precision
If tumor tissue complexity is maintained (including immune and stromal cells), then measurement precision is improved, but device complexity and culture difficulty worsen
Solution Approach 1:
The organoid culture system enables tumor cells to self-organize into three-dimensional structures that automatically recapitulate the tumor microenvironment architecture. The cells self-assemble with stromal and immune components in their native spatial relationships, eliminating the need for complex manual construction of the tissue model while preserving biological fidelity.
Solution Approach 2:
The patent employs specific culture parameters (three-dimensional geometry, extracellular matrix composition, growth factor concentrations, oxygen gradients) that guide the self-organization of tumor cells into functional organoids. By optimizing these physical and chemical parameters, the system maintains tissue complexity without requiring equally complex intervention protocols.
Data Source
Figure 1A~1D
Figure 1E~1G
Figure 1H~1J
AI summary
Described herein are methods and systems for evaluating cell samples, including tissue samples such as cancer tissue. In some cases, evaluating cell samples comprises longitudinal evaluation of one or more candidate molecules. Methods and systems for assessing cellular viability are provided.