Antigen-Specific T Cell Receptor Isolation for Immunotherapy
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Solution Overview
Problem
Current immunotherapy approaches for cancer and infectious diseases face challenges in generating antigen-specific T cells, particularly due to the laborious process of establishing T cell clones for TCR gene isolation and the limited number of suitable TCR candidates available for broad antigen and MHC restrictions.
Innovation Solution
A method involving the isolation of a single antigen-reactive T cell, encoding its T cell receptor, and introducing this nucleic acid into lymphoid cells to create antigen-specific lymphoid cells with defined MHC restriction, enabling the identification of immunologically relevant T cell epitopes and broad applicability of adoptive TCR transfer.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If traditional methods of establishing T cell clones for TCR gene isolation are used, then antigen-specific T cells can be obtained, but the process is laborious and time-consuming
Solution Approach 1:
The patent extracts and isolates the T cell receptor (TCR) gene from a single antigen-reactive T cell, then transfers this specific gene into lymphoid cells. This extraction approach bypasses the laborious process of establishing complete T cell clones while obtaining the essential antigen-specific component (TCR gene) for immunotherapy applications.
Solution Approach 2:
The invention segments the T cell into its critical functional component - the TCR gene - which can be isolated, characterized, and transferred independently. This segmentation allows obtaining antigen-specific T cells without going through the entire T cell clone establishment process, significantly reducing time and effort.
2Productivity
If a limited number of TCR candidates are used, then the process is simplified, but the applicability to broad antigens and MHC restrictions is reduced
Solution Approach 1:
The patent performs preliminary characterization of the TCR gene's antigen specificity and MHC restriction properties before transfer. This preliminary action enables the selection of TCR candidates with desired characteristics, allowing efficient generation of antigen-specific T cells while maintaining broad applicability to different antigens and MHC restrictions.
Solution Approach 2:
The invention changes the parameters of TCR selection by characterizing and selecting based on antigen specificity and MHC restriction properties. This parameter-based selection approach enables broadening the applicability of TCR candidates across different antigens and MHC types while maintaining efficient T cell generation.
3Quantity of substance
If TCR genes are transferred into lymphoid cells to create antigen-specific cells, then the availability of suitable TCR candidates is improved, but the complexity of the gene isolation and transfer process increases
Solution Approach 1:
The patent creates copies of the TCR gene from a single antigen-reactive T cell and introduces these copies into multiple lymphoid cells. This copying approach increases the quantity of available TCR candidates and enables generation of antigen-specific T cells without requiring complex isolation and transfer procedures for each individual cell.
Data Source
AI summary
The present invention relates to efficient methods for providing antigen-specific lymphoid cells. These lymphoid cells may be used to provide antigen specific T cell receptors having a defined MHC restriction and to identify immunologically relevant T cell epitopes. Furthermore, the present invention relates to antigen-specific T cell receptors and T cell epitopes and their use in immunotherapy.