T Cell Anergy Identification via Gene Expression Profiling

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Solution Overview

Problem

Current understanding of T cell anergy is incomplete due to the lack of surface markers for identifying anergic T cells and the unclear mechanisms by which T cells subjected to anergy-inducing conditions are not deleted, particularly in relation to tumor susceptibility to immunotherapy.

Innovation Solution

Methods and compositions are provided for evaluating and treating T cell anergy by measuring the expression levels of specific genes associated with T cell anergy, using nucleic acid molecules to reduce gene expression or activity, and administering immunotherapy or T cell anergy suppressors to modulate T cell responses.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If T cell anergy is induced by TCR engagement without costimulation, then T cell hyporesponsiveness is achieved, but the mechanism of T cell survival without deletion remains unclear

Engineering Contradiction:

ImproveT cell hyporesponsivenessVSAvoidmechanism understanding

Core Design Contradiction:

ReliabilityVSLoss of information

Solution Approach 1:

The patent employs gene expression profiling to measure the expression levels of multiple genes (including EGR2, DGKα, DGKζ, Cbl-b, GRAIL, Itch, Deltex1, and Tob1) in T cells, creating a feedback mechanism that reveals the molecular signature of anergy. This systematic measurement approach uncovered that EGR2 transcriptionally regulates most anergy-associated genes, providing the missing mechanistic information about how anergic T cells survive without deletion.

Inventive Principle:

Principle #23Feedback

2Measurement precision

If surface markers are used to identify anergic T cells, then identification accuracy is improved, but no surface markers currently exist for anergic T cells

Engineering Contradiction:

Improveanergic T cell identificationVSAvoididentification method

Core Design Contradiction:

Measurement precisionVSDevice complexity

Solution Approach 1:

The patent replaces the need for surface marker-based identification (mechanical/physical detection) with gene expression-based identification (molecular detection). By measuring the expression levels of specific genes (EGR2, DGKα, DGKζ, Cbl-b, GRAIL, Itch, Deltex1, Tob1) through molecular biology techniques such as RT-PCR or microarray analysis, the patent achieves precise identification of anergic T cells without requiring surface markers, thereby substituting a molecular detection system for a phenotypic detection system.

Inventive Principle:

Principle #28Mechanics substitution (Replace mechanical system)

3Productivity

If Egr2 is upregulated upon anergy induction, then anergy-associated gene transcription is promoted, but the comprehensive target genes of Egr2 were not previously identified

Engineering Contradiction:

Improvegene transcription efficiencyVSAvoidtarget gene repertoire

Core Design Contradiction:

ProductivityVSLoss of information

Solution Approach 1:

The patent demonstrates that EGR2 serves as a universal transcriptional regulator for multiple anergy-associated genes simultaneously. Through gene expression profiling and transcription factor binding assays, the patent identified that EGR2 regulates DGKα, DGKζ, Cbl-b, GRAIL, Itch, Deltex1, and Tob1, revealing its multi-functional role in coordinating the transcriptional program of T cell anergy. This universal regulatory function explains how a single transcription factor can orchestrate the expression of multiple anergy-associated genes.

Inventive Principle:

Principle #6Universality (Multi-functionality)

Data Source

PatentUS20240102107A1Methods and compositions related to t-cell activity

Publication Date: 2024.03.28 UNIVERSITY OF CHICAGO

AI summary

Embodiments concern methods and composition related to anergic T-cells in patients, such as cancer patients.