CD127lowPD-1low T Cell Quantification for Immunotherapy Response
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Solution Overview
Problem
Current cancer immunotherapy methods are ineffective for many patients, particularly those with adenocarcinomas, due to a lack of understanding of the global immune dynamics that mediate anti-tumor immunity and the anatomical sites where immune cell activation occurs.
Innovation Solution
A computer-implemented method using mass cytometry to assess the immune state by quantifying CD127lowPD-1low T cells, allowing for the identification and monitoring of cancer patients amenable to anti-cancer immunotherapy, specifically with anti-CTLA-4 antibodies, and providing a therapeutically effective composition for treating melanoma.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional immunotherapy is administered to cancer patients, then treatment is provided, but most patients do not respond to the therapy
Solution Approach 1:
The patent performs preliminary characterization of the immune system state before immunotherapy administration by measuring multiple immune parameters (T cell subsets, cytokines, chemokines). This preliminary assessment identifies patients likely to respond to immunotherapy, enabling selective treatment administration to improve response rates while maintaining broad applicability across different cancer types and patient populations.
2Loss of information
If comprehensive immune dynamics are studied to improve immunotherapy, then understanding of anti-tumor immunity improves, but the complexity of the immune system makes comprehensive understanding difficult
Solution Approach 1:
The patent segments the complex immune system into measurable components and parameters, including specific T cell subsets (CD4+, CD8+, Treg), cytokines (IL-2, IFN-gamma, TNF-alpha), and chemokines. By measuring these discrete segments separately through flow cytometry and ELISA, the patent simplifies the analysis of global immune dynamics while maintaining comprehensive understanding capability.
Solution Approach 2:
The patent creates a universal immune characterization protocol that can be applied across different cancer types, patient populations, and treatment contexts. The same set of immune parameters and measurement techniques serve multiple functions: predicting immunotherapy response, monitoring treatment efficacy, and understanding immune dynamics in various anatomical sites, thereby reducing the complexity burden through multi-purpose application.
3Loss of information
If immune cell activation sites are investigated, then anatomical understanding of anti-tumor immunity improves, but the location of immune cell activation remains unclear
Solution Approach 1:
The patent transitions from asking where immune activation occurs to measuring the functional state of immune cells across multiple anatomical sites simultaneously. By characterizing immune parameters in blood, tumor tissue, and lymph nodes, the patent creates a multi-dimensional view of immune activation that resolves the location problem through functional assessment rather than single-site anatomical focus.
Data Source
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AI summary
Methods for identifying cancer patients amenable to anti-cancer immunotherapy are provided along with methods of monitoring cancer therapy. Also provided are methods of treating cancer patients amenable to anti-cancer immunotherapy. The methods involve determining the level of CD127 <low> PD-1 <low> T cells. The patients are treated with an immune checkpoint inhibitor, such as an anti-CTLA-4 antibody, e.g. ipilimumab.