In Vivo Passaging for Cancer Stem Cell Marker Identification
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Solution Overview
Problem
Current methods are inadequate for effectively identifying and targeting cancer stem cells in primary tumors, particularly in aggressive pediatric cancers like atypical teratoid/rhabdoid tumors, which hinders diagnosis and treatment efficacy.
Innovation Solution
A method involving in vivo passaging of primary tumors to enrich and identify cancer stem cell markers by comparing antigen levels in passaged and non-passaged tumor cells, allowing for the selection of therapeutic agents that downregulate these markers.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If current methods are used to identify cancer stem cells, then the diagnostic process is simple, but the identification accuracy and treatment targeting capability are insufficient
Solution Approach 1:
The patent segments the tumor population by performing in vivo passaging to separate cancer stem cells (which can propagate tumors) from non-stem cancer cells. This segmentation enables precise identification of CSCs through their unique ability to initiate tumor growth in immunodeficient mice, directly resolving the contradiction between identification accuracy and method simplicity.
Solution Approach 2:
The patent applies preliminary action by pre-enriching cancer stem cells through multiple in vivo passaging cycles before analysis. By repeatedly transplanting tumor cells into immunodeficient mice and isolating propagating cells, the method concentrates CSCs in advance, improving subsequent identification accuracy without requiring complex diagnostic equipment.
2Manufacturing precision
If in vivo passaging is performed to enrich cancer stem cells, then the purity of cancer stem cell population increases, but the time and number of passages required increase
Solution Approach 1:
The patent employs periodic action by conducting in vivo passaging at regular intervals (multiple cycles of transplantation into immunodeficient mice). This periodic enrichment process gradually increases CSC population purity with each cycle, balancing the need for high purity with the constraint of time by using standardized, repeatable cycles rather than continuous optimization.
Solution Approach 2:
The patent uses copying by transplanting tumor cells into immunodeficient mice to create xenograft models that replicate the original tumor's CSC population. This copying process allows enrichment of CSCs in a controlled environment without requiring extensive in vitro manipulation, reducing time loss while achieving high population purity.
3Reliability
If markers are identified in passaged tumor cells, then the therapeutic targeting capability improves, but the complexity of treatment selection increases
Solution Approach 1:
The patent applies feedback by using identified CSC markers (such as CD133, CD44, ALDH1) to guide therapeutic agent selection. The markers provide feedback information about the presence and characteristics of CSCs in the patient's tumor, enabling clinicians to select treatments specifically targeting these markers, thereby improving treatment efficacy while maintaining a manageable selection process through standardized marker-based protocols.
Data Source
AI summary
A method of identifying cancer stem cell markers in a human primary tumor is disclosed. The method comprises:(a) in vivo passaging the primary tumor; and(b) comparing a level of at least one antigen in a first population of passaged tumor cells of the primary tumor with a second population of tumor cells of the primary tumor,wherein an increase in the amount of the antigen in the first population of tumor cells as compared to the amount of the antigen in the second population of tumor cells is indicative of a cancer stem cell marker in the human primary tumor.