Tumor-Specific CD8+ T Cell Identification Using CD82 Marker Profiles
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current methods for identifying and isolating mutation-related or tumor-specific CD8+ T cells require knowledge of specific antigens and are labor-intensive, making them inefficient and unreliable for predicting responses to immune checkpoint inhibitor therapy and prone to side effects.
Innovation Solution
A method for identifying mutation-related CD8+ T cells by analyzing the expression of markers CD82, CD11a, CD18, and CD43, allowing for the isolation of these cells without prior knowledge of specific antigens, using flow cytometry or magnetic activated cell sorting.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If current methods for identifying tumor-specific T cells using antigen-specific techniques are used, then measurement precision is improved, but device complexity and loss of time increase significantly
Solution Approach 1:
The invention changes the identification parameters from antigen-specific recognition to marker expression patterns (CD82, CD11a, CD18, CD43). By monitoring expression levels and combinations of these markers, the method identifies tumor-specific T cells through phenotypic characteristics rather than requiring antigen-specific binding assays, thereby reducing complexity while maintaining identification accuracy
Solution Approach 2:
The identified marker profile (CD82, CD11a, CD18, CD43) serves multiple functions: it identifies tumor-specific T cells, predicts response to checkpoint inhibitor therapy, and enables isolation of these cells for adoptive transfer. This universal marker set replaces multiple specialized antigen-specific assays with a single multi-functional identification system
2Measurement precision
If current antigen-specific identification methods are used, then measurement precision is improved, but loss of time increases due to labor-intensive procedures
Solution Approach 1:
The invention replaces manual, labor-intensive antigen-specific assays with automated flow cytometry or magnetic-activated cell sorting based on marker expression. This substitution of mechanical/manual procedures with automated instrumental analysis dramatically reduces identification time while maintaining precision through objective, quantifiable marker measurement
3Reliability
If current identification methods are used, then reliability of therapy prediction is improved, but object-generated harmful factors increase due to side effects
Solution Approach 1:
The invention performs preliminary identification and isolation of tumor-specific T cells using the marker profile before initiating checkpoint inhibitor therapy or adoptive transfer. This preliminary characterization ensures that only appropriately selected cells are used, improving therapy prediction reliability and reducing adverse effects by avoiding inappropriate therapeutic interventions
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
Enables efficient and reliable identification and isolation of mutation-related CD8+ T cells, facilitating effective adoptive T cell transfer therapy and early prediction of immune checkpoint inhibitor therapy response, while minimizing side effects.
Implementation Method 1
using flow cytometry or magnetic activated cell sorting
Implementation Method 2
using flow cytometry or magnetic activated cell sorting
Data Source
Figure 1Aa~1B
Figure 2A~2C
Figure 2D~2E
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, CD18 or CD43. A preferred marker for mutation-related CD8+ T cells is CD82, which may be analysed in combination with CD11a, CD18 or CD43. 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 T cells that are (i) CD8 +, (ii) either CD82 hi, CD194 hi, CD244 -, CD28 +, CD62L + and/or CD55 + and (iii) CD11a hi, CD18 hi and/or CD43 hi 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.