CD82 Marker Profiling for Tumor-Specific CD8+ T Cell Isolation
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Solution Overview
Problem
Current methods for identifying and isolating mutation-related or tumor-specific CD8+ T cells are cumbersome and require knowledge of specific antigens or imaging, with low response rates to checkpoint inhibitor therapy and significant side effects, lacking reliable biomarkers for patient selection.
Innovation Solution
A method analyzing the expression of markers CD82, CD194, CD244, CD28, CD62L, and CD55 on CD8+ T cells to identify mutation-related T cells, allowing for their isolation and potential use in cancer treatment without requiring antigen identification.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If current methods for identifying tumor-specific T cells are used, then specific tumor antigens can be targeted, but the process is cumbersome and requires prior knowledge of specific antigens
Solution Approach 1:
The invention changes the identification parameters from antigen-specific markers to surface marker expression profiles (CD82, CD194, CD244, CD28, CD62L, CD55). By analyzing the expression pattern of these six markers, the method identifies mutation-related T cells without requiring prior knowledge of tumor antigens, thus simplifying the identification process while maintaining accuracy
Solution Approach 2:
The invention creates a universal identification method that works across different tumor types and patients. The six-marker panel can identify mutation-related T cells in various cancer contexts without needing tumor-specific antigen information, making the method broadly applicable rather than limited to specific antigen-known scenarios
2Reliability
If checkpoint inhibitor therapy is administered to all cancer patients, then some patients may benefit, but the overall response rate is low and side effects are significant
Solution Approach 1:
The invention enables preliminary identification of mutation-related T cells before initiating checkpoint inhibitor therapy. By analyzing the six-marker expression profile in advance, clinicians can select patients who are more likely to respond to therapy, thereby improving overall therapeutic efficacy while reducing unnecessary exposure to side effects in non-responders
3Measurement precision
If traditional T cell identification methods are used, then antigen-specific T cells can be identified, but reliable biomarkers for patient selection are lacking
Solution Approach 1:
The invention introduces a new set of six biomarkers (CD82, CD194, CD244, CD28, CD62L, CD55) for identifying mutation-related T cells. This marker panel provides reliable, quantifiable parameters for patient selection and therapy response prediction, replacing the lack of available biomarkers with a comprehensive six-parameter assessment system
Data Source
AI summary
The present invention relates to the field of tumor immunology. It provides a method for identifying mutation-related human CD8+ T cells, in particular, tumor-specific T cells of a human subject, comprising analyzing CD8+ T cells of the subject by analysing the expression of at least one marker selected from a first group consisting of CD82, CD194, CD244, CD28, CD62L and CD55, and preferably, a marker selected from a second group comprising CD11a or CD18 or CD43. A preferred marker for mutation-related CD8+ T cells is CD82, which may be analysed in combination, e.g., with CD11a. Without the need to identify any epitope to which T cells reacts, this method can advantageously be used to isolate the entire individual pool of mutation-related T cells, and, optionally, to identify the sequence of a mutation-related TCR, which allows for generation of transgenic T cells expressing the TCR. Compositions substantially comprising tumor-specific CD82hiCD8+ T cells and/or CD194hi, CD244−, CD28+, CD62L+ and/or CD55+ CD82hiCD8+ T cells can be used for treatment of a cancer patient, e.g., by adoptive T cell transfer. The method of the invention can also be used for diagnostic purposes to identify human mutation-related T cells or diagnosing a tumor disease or for testing responses of a cancer patient to an immune stimulatory therapy, preferably, a therapy with a checkpoint inhibitor.