Combined TCR and HLA Profiling Kit for Immune Response Monitoring

Resolve Bottlenecks,
Find Innovative SolutionsGenerate Solutions

Solution Overview

Problem

Current diagnostic methods for immune responses are limited by the need for separate and time-consuming HLA typing and TCR profiling, which do not reflect in vivo HLA status and require significant sample amounts, preventing simultaneous analysis of TCR repertoires and HLA isotypes.

Innovation Solution

A method and kit for combined profiling of αβ-TCR repertoires and HLA isotypes using gene expression profiles derived from mRNAs encoding MHC and T cell receptor chains, allowing simultaneous analysis of T cell receptor expression and HLA expression in a single assay.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Loss of information

If separate HLA typing and TCR profiling methods are used, then comprehensive immune response information can be obtained, but the diagnostic process becomes time-consuming and requires significant sample amounts

Engineering Contradiction:

Improvecomprehensive immune response informationVSAvoiddiagnostic process time

Core Design Contradiction:

Loss of informationVSLoss of time

Solution Approach 1:

The patent combines separate HLA typing and TCR profiling procedures into a single integrated assay that simultaneously analyzes both MHC class I/II molecules and T cell receptor repertoires from the same biological sample, eliminating the need for separate testing procedures and reducing overall diagnostic time

Inventive Principle:

Principle #5Merging (Combining)

Solution Approach 2:

The invention creates a universal diagnostic platform using next-generation sequencing technology that can simultaneously perform multiple functions: HLA genotype determination, MHC class I/II expression profiling, and TCR repertoire analysis from a single sample input, making the system multi-functional and highly efficient

Inventive Principle:

Principle #6Universality (Multi-functionality)

2Measurement precision

If traditional HLA typing and TCR profiling are performed separately, then detailed immune analysis is possible, but the requirement for significant sample amounts becomes a limitation

Engineering Contradiction:

Improveimmune analysis detailVSAvoidsample amount required

Core Design Contradiction:

Measurement precisionVSQuantity of substance

Solution Approach 1:

By merging HLA typing and TCR profiling into a single NGS-based assay, the patent reduces the total sample material required compared to performing separate analyses, as the integrated method efficiently utilizes the available RNA to generate comprehensive immune profile data

Inventive Principle:

Principle #5Merging (Combining)

3Loss of information

If separate HLA typing and TCR profiling assays are used, then comprehensive immune data can be collected, but the overall diagnostic cost increases

Engineering Contradiction:

Improveimmune data comprehensivenessVSAvoiddiagnostic cost

Core Design Contradiction:

Loss of informationVSEase of manufacture

Solution Approach 1:

The patent employs a universal next-generation sequencing platform that performs HLA typing, MHC expression profiling, and TCR repertoire analysis in a single run, eliminating the need for multiple separate assays and thereby reducing the cumulative cost of reagents, equipment usage, and processing time

Inventive Principle:

Principle #6Universality (Multi-functionality)

4Measurement precision

If traditional separate assays for HLA and TCR analysis are performed, then detailed immune profiling is achieved, but the complexity of the diagnostic workflow increases

Engineering Contradiction:

Improveimmune profiling detailVSAvoiddiagnostic workflow complexity

Core Design Contradiction:

Measurement precisionVSDevice complexity

Solution Approach 1:

The patent merges multiple complex separate assays into a single integrated NGS workflow, simplifying the diagnostic process by eliminating the need for separate sample preparations, multiple sequencing runs, and independent data analysis pipelines for HLA and TCR analysis

Inventive Principle:

Principle #5Merging (Combining)

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 unbiased, cost-effective, and time-efficient monitoring of immune responses, particularly in cancer patients, by providing comprehensive information on TCR repertoires and HLA status, facilitating personalized therapies and distinguishing tumor cells with down-regulated HLA alleles.

Implementation Method 1

establishing gene expression profiles of a first and a second sample, wherein said establishing of gene expression profiles comprises: (i) identifying and quantifying mRNAs encoding MHC class I (MHC I) or MHC class II (MHC II) isotypes and (ii) identifying and quantifying mRNAs encoding T cell receptor chains transcribed from recombined T cell receptor loci

Methodology Applied

Scientific EffectGene expression profiling:

Data Source

PatentUS10550430B2Method and kit for determining whether a subject shows an immune response

Publication Date: 2020.02.04 TRON TRANSLATIONALE ONKOLOGIE AN DER UNIVERSITAETSMEDIZIN DER JOHANNES GUTENBERG UNIV MAINZ GEMEINNUETZIGE GMBH

AI summary

The present invention relates to a kit and a method for determining whether a subject shows an immune response against an antigen.