T Cell Gene Expression Analysis for Therapy Prediction

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Solution Overview

Problem

Current CAR T cell therapies face challenges in predicting individual patient responsiveness, leading to variable treatment outcomes, and there is a need for methods to enhance T cell functionality and predict suitability for different therapies.

Innovation Solution

A method involving determining gene expression levels of DNMT3A methylation targets in T cells, generating a Diagnostic Expression Score, and using this score to predict responsiveness to autologous or allogeneic T cell therapies, with options to improve T cell functioning by inhibiting DNMT3A-mediated methylation and activating the STAT5 signaling pathway.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If CAR T cell therapy is administered to patients, then cancer treatment is provided, but prediction of individual patient responsiveness is poor leading to variable treatment outcomes

Engineering Contradiction:

Improvetreatment outcome prediction accuracyVSAvoidpatient responsiveness information

Core Design Contradiction:

ReliabilityVSLoss of information

Solution Approach 1:

The patent performs gene expression analysis of DNMT3A target genes in T cells before administering CAR T cell therapy to predict patient responsiveness. This preliminary assessment allows clinicians to identify patients likely to respond to therapy versus those who may not benefit, enabling informed treatment decisions before the actual therapy is given.

Inventive Principle:

Principle #10Preliminary action

Solution Approach 2:

The patent replaces empirical, trial-and-error treatment selection with a molecular biology-based predictive system. By measuring gene expression levels of DNMT3A target genes and calculating a diagnostic score, the system objectively predicts treatment responsiveness without relying on mechanical observation of treatment outcomes after administration.

Inventive Principle:

Principle #28Mechanics substitution (Replace mechanical system)

2Reliability

If T cell functionality is enhanced through DNMT3A inhibition and STAT5 activation, then T cell therapy effectiveness is improved, but treatment complexity increases

Engineering Contradiction:

ImproveT cell therapy effectivenessVSAvoidtreatment protocol complexity

Core Design Contradiction:

ReliabilityVSDevice complexity

Solution Approach 1:

The patent modifies biochemical parameters within T cells by inhibiting DNMT3A enzyme activity (reducing DNA methylation) and activating STAT5 signaling pathway. These parameter changes at the molecular level enhance T cell functionality, persistence, and therapeutic effectiveness without requiring complex external devices or procedures.

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent uses small molecule inhibitors of DNMT3A and activators of STAT5 signaling as intermediary substances to modify T cell behavior. These chemical mediators interact with specific molecular targets within T cells to achieve desired functional enhancements, providing a controllable and reversible approach to improving therapy effectiveness.

Inventive Principle:

Principle #24Intermediary (Mediator)

Data Source

PatentUS20220326216A1T cell gene expression analysis for use in t cell therapies

Publication Date: 2022.10.13 ST JUDE CHILDRENS RES HOSPITAL INC

AI summary

The application provides T cell gene expression signatures that can be used to predict T cell therapy outcomes.