T-Cell Biomarker Screening for Predictive Adoptive Immunotherapy
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Solution Overview
Problem
The efficiency of adoptive immunotherapy varies significantly from cell sample to cell sample, necessitating methods to predict the therapeutic efficacy of immunotherapeutic samples, particularly for diseases like progressive multiple sclerosis.
Innovation Solution
A method is developed to select T cells for adoptive immunotherapy by incubating them with antigen-presenting cells presenting LMP1, LMP2A, and EBNA1 epitopes, and assessing the expression of IFNg, CD107a, IL-2, TNF, and CD8 to identify T cells specific for Epstein-Barr Virus peptides, ensuring at least 1% of lymphocytes express these markers and 20% express CD8, using techniques like FACS or ELISpot.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If T cell samples are selected without predictive markers, then the selection process is simple and quick, but the therapeutic efficacy varies significantly and cannot be predicted
Solution Approach 1:
The patent performs preliminary assessment of T cell samples by incubating with antigen-presenting cells and measuring marker expression (IFNg, CD107a, IL-2, TNF, CD8) before adoptive immunotherapy. This preliminary action predicts therapeutic efficacy in advance, allowing selection of samples with at least 1% expressing cytokine markers and 20% expressing CD8, thereby ensuring reliable treatment outcomes before administration.
2Reliability
If multiple marker expression thresholds are required (1% for IFNg, CD107a, IL-2, TNF and 20% for CD8), then the therapeutic potential is enhanced, but the selection criteria become more complex and harder to detect
Solution Approach 1:
The patent divides the T cell assessment into separate measurable components: incubation with antigen-presenting cells presenting specific epitopes, followed by individual measurement of each marker (IFNg, CD107a, IL-2, TNF, CD8) using techniques like FACS or ELISpot. This segmentation allows complex multi-marker assessment to be performed systematically, with clear thresholds (1% for cytokine markers, 20% for CD8) that can be detected and measured independently.
Data Source
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AI summary
Provided herein are methods and compositions related to the selection T cells and/or subjects for adoptive immunotherapy based on the expression of one or more biomarkers selected from granzyme B, granzyme K, perforin, CD8, PD-1, TIM-3, LAG-3, CTLA-4, CD107a, IFNg, IL-2, TNF and CD4.