T Cell Receptor Isolation via Gene Expression Profiling
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current methods for isolating cancer-reactive T cells are time-consuming and inefficient, often failing to identify the desired T cell receptors that bind specifically to cancer targets, limiting the effectiveness of adoptive cell therapy for cancer treatment.
Innovation Solution
A method involving the isolation of T cells from tumor samples, followed by gene expression profiling and sequencing to identify and enrich populations with specific antigenic specificity, allowing for the reconstruction and isolation of T cell receptors (TCRs) with antigenic specificity for cancer-specific or viral antigens.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If current methods are used to produce cancer-reactive T cells, then T cell therapy can be provided, but the process requires significant time and may not readily identify the desired T cell receptors
Solution Approach 1:
The patent applies preliminary action by performing gene expression profiling and T cell receptor sequencing on tumor-infiltrating T cells before adoptive cell therapy. This allows identification of cancer-reactive T cells and their specific targets in advance, enabling more rapid and targeted therapy production without extensive subsequent screening
Solution Approach 2:
The patent replaces traditional mechanical screening methods with molecular analysis techniques. By using gene expression profiling and TCR sequencing to identify cancer-reactive T cells, the method substitutes direct functional screening with molecular characterization, significantly reducing the time required to identify therapeutic T cell populations
2Loss of information
If traditional isolation methods are used, then T cells can be obtained, but the desired T cell receptors that bind cancer targets are not readily identified
Solution Approach 1:
The patent uses gene expression profiles and T cell receptor sequences as intermediary markers to identify cancer-reactive T cells. These molecular intermediaries provide information about T cell specificity without requiring direct functional testing, enabling efficient isolation of therapeutic T cells while preserving information about their target recognition capabilities
Solution Approach 2:
The patent changes the parameters used for T cell identification from phenotypic markers to molecular parameters including gene expression profiles and TCR sequences. This parameter change enables direct identification of cancer-reactive T cells based on their molecular characteristics rather than requiring functional screening, thereby preventing loss of specificity information while improving isolation efficiency
Data Source
AI summary
Provided are methods of preparing an enriched population of T cells having antigenic specificity for a target antigen. The method may comprise isolating T cells from a tumor sample of a patient; selecting the isolated T cells which have a gene expression profile; and separating the selected T cells from the unselected cells. The separated selected T cells provide an enriched population of T cells having antigenic specificity for the target antigen. Methods of isolating a T cell receptor (TCR), preparing a population of cells that express a TCR, isolated TCRs, isolated populations of cells, pharmaceutical compositions, and methods of treating or preventing a condition in a mammal are also provided.