Ex Vivo Tumor Biopsy Stress Testing for Immunotherapy Selection
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Solution Overview
Problem
Current cancer therapies face limitations due to inconsistent immune responses and immune evasion mechanisms, as existing methods fail to account for the variability of neoepitopes and stress markers on cancer cells, leading to unpredictable treatment outcomes and resistance to specific drugs.
Innovation Solution
The method involves exposing tumor biopsy samples to various stress conditions ex vivo to increase immunogenicity, followed by contact with immune competent cells to quantify responses, selecting stress conditions that meet a predetermined threshold, and potentially using immune stimulants and neoepitope identification to enhance immune activation.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If immunotherapy is used to eradicate cancer cells, then immune response is stimulated, but treatment outcomes are unpredictable due to variability in neoepitopes and immune evasion mechanisms
Solution Approach 1:
The patent applies preliminary action by exposing tumor cells to stress conditions before immunotherapy to pre-modify their immunogenicity. This pre-treatment with stressors (e.g., chemotherapy, radiation, hypoxia) induces expression of stress markers and neoepitopes in advance, making the tumor cells more recognizable to the immune system before the actual immunotherapy is administered, thereby reducing the unpredictability of treatment outcomes
Solution Approach 2:
The patent employs parameter changes by systematically varying stress conditions (type, duration, intensity) to which tumor cells are exposed, thereby changing the immunogenic parameters of the tumor cells. This includes modifying the expression levels of stress markers and neoepitopes through controlled stress exposure, which in turn alters how the immune system recognizes and responds to the tumor cells
2Measurement precision
If personalized medicine based on genomic or proteomic insights is used, then treatment targeting is improved, but the number of effective treatment options remains limited
Solution Approach 1:
The patent applies segmentation by dividing the tumor biopsy into multiple sub-samples and exposing each to different stress conditions. This allows simultaneous evaluation of multiple treatment scenarios from a single biopsy, generating a broader range of treatment options while maintaining precise tumor characterization through comprehensive stress marker and neoepitope profiling across different stress conditions
Solution Approach 2:
The patent implements universality by creating a multi-functional assay system that can evaluate multiple potential treatments (different stress conditions) using a single biopsy sample. The system simultaneously assesses tumor cell response to various stressors and predicts immunogenicity outcomes, providing diverse treatment recommendations from one comprehensive test
3Reliability
If stress conditions are applied to increase immunogenicity, then immune recognition is enhanced, but tumor cell viability may be compromised
Solution Approach 1:
The patent applies partial action by using sub-lethal doses of stress conditions that are sufficient to induce immunogenic changes (stress marker expression, neoepitope presentation) without completely compromising tumor cell viability. This allows the tumor cells to remain alive and present antigens to the immune system while still being sufficiently modified to enhance immune recognition and facilitate subsequent immune-mediated eradication
Data Source
AI summary
Ex vivo determination of increased tumor immunogenicity of a tumor biopsy is used as a guide to identify immunotherapy of a tumor in a patient. Most preferably, the ex vivo tests will include exposure of biopsy samples to stress conditions to produce pretreated tumor cells that are then assayed with immune competent cells for increased activation or activity. Test conditions include exposure of the biopsy samples to immune stimulatory compositions, antibodies against neoepitopes, and/or modified cells, and an increase of immunogenicity is preferably determined by their exposure to T cells and/or NK cells.