Eomes Memory T-Cell Profiling to Guide Allograft Rejection Therapy

Resolve Bottlenecks,
Find Innovative SolutionsGenerate Solutions

Solution Overview

Problem

Pre-existing alloreactive memory T cells pose a significant barrier to the induction of allograft tolerance in organ transplant recipients, particularly in non-human primate models and clinical transplantation, and current immunosuppressive therapies like CTLA4Ig have shown increased rejection rates and may prevent regulatory T cell-dependent transplant tolerance.

Innovation Solution

Measuring Eomesodermin (Eomes) expression in memory T cells to predict the risk of allograft rejection and modify immunosuppressive therapy based on the detected Eomes levels, including adjusting the dose or type of immunosuppressive agents.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If CTLA4Ig (belatacept) is used to block the B7-CD28 pathway, then co-stimulation blockade is achieved, but the incidence of acute cellular rejection increases and regulatory T cell-dependent transplant tolerance is prevented

Engineering Contradiction:

Improvetransplant toleranceVSAvoidacute cellular rejection

Core Design Contradiction:

ReliabilityVSObject-generated harmful factors

Solution Approach 1:

The patent changes the parameter of T cell differentiation by measuring Eomes expression levels to identify and target specific EomesloCTLA4hiCD8+ T cell subsets that are resistant to co-stimulation blockade, allowing for personalized immunosuppressive therapy adjustments that overcome the limitations of CTLA4Ig

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent implements feedback by measuring Eomes expression in memory T cells to predict rejection risk and monitor therapy effectiveness, enabling dynamic modification of immunosuppressive therapy based on real-time biomarker data

Inventive Principle:

Principle #23Feedback

2Reliability

If pre-existing alloreactive memory T cells are present, then the barrier to induction of tolerance is established, but the ability to achieve transplant tolerance is reduced

Engineering Contradiction:

Improvetransplant tolerance inductionVSAvoidalloreactive memory T cells

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent extracts and targets the harmful EomesloCTLA4hiCD8+ T cell subset from the broader memory T cell population, identifying them as the specific subset responsible for co-stimulation blockade resistance and prioritizing them for therapeutic intervention

Inventive Principle:

Principle #2Taking out (Extraction)

Solution Approach 2:

The patent utilizes Eomes expression levels as a differentiating parameter to identify and target the specific subset of memory T cells that pose the greatest threat to transplant tolerance, enabling precision therapy against the harmful subset while preserving beneficial T cell functions

Inventive Principle:

Principle #35Parameter changes

Data Source

PatentUS12372513B2Use of eomesodermin to determine risk of allograft rejection

Publication Date: 2025.07.29 UNIV OF PITTSBURGH OF THE COMMONWEALTH SYST OF HIGHER EDUCATION

AI summary

Pre-existing alloreactive memory T cells are a major barrier to the induction of allograft tolerance in organ transplant recipients. The use of Eomesodermin (Eomes) expression in memory T cells to determine the risk of allograft rejection in a subject is described. Also described is the use of Eomes expression in memory T cells of transplant recipients to modify immunosuppressive therapy.