CD3+CD4+CD57+ILT2+ T Cells for Early CLAD Prediction

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Solution Overview

Problem

Current treatments for Chronic Lung Allograft Dysfunction (CLAD) in lung transplant patients are ineffective due to late-stage diagnosis and irreversible fibro-proliferative lesions, lacking validated early markers for predicting CLAD occurrence, which hinders timely adaptation of immunosuppressive treatments.

Innovation Solution

Identification and characterization of a novel human T cell sub-population, CD3+CD4+CD57+ILT2+, which serves as a non-invasive biomarker for predicting CLAD and exhibits cytotoxic effects, allowing for early identification of at-risk patients and potential therapeutic targeting.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If current treatments for CLAD are administered, then they can address symptomatic patients, but they are ineffective because diagnosis occurs at late stage when fibro-proliferative lesions are already irreversible

Engineering Contradiction:

Improvetreatment effectivenessVSAvoiddiagnosis timing

Core Design Contradiction:

ReliabilityVSLoss of time

Solution Approach 1:

The patent applies preliminary action by identifying and monitoring CD4+CD57+ T cells as an early biomarker before clinical symptoms of CLAD appear. This allows prediction of CLAD occurrence in advance, enabling intervention before irreversible fibro-proliferative lesions develop, thus resolving the timing contradiction between early detection and treatment effectiveness

Inventive Principle:

Principle #10Preliminary action

2Measurement precision

If spirometric functional impairment is used for diagnosis, then CLAD can be identified, but it is of limited clinical interest because the fibro-proliferative bronchiolar lesions are already irreversible at this stage

Engineering Contradiction:

Improvediagnosis accuracyVSAvoiddisease progression stage

Core Design Contradiction:

Measurement precisionVSLoss of time

Solution Approach 1:

The patent uses CD4+CD57+ T cell monitoring as a preliminary diagnostic tool that detects pre-clinical immune responses before spirometric impairment occurs. This early biomarker approach maintains diagnostic accuracy while advancing the detection timeline to the pre-symptomatic stage, avoiding the limitation of late-stage diagnosis

Inventive Principle:

Principle #10Preliminary action

3Reliability

If routine post-transplant transbronchial biopsy surveillance is performed, then graft monitoring is provided, but it is not useful for early diagnosis of CLAD due to frequent false-negative histology results and invasive nature

Engineering Contradiction:

Improvesurveillance reliabilityVSAvoiddiagnosis invasiveness

Core Design Contradiction:

ReliabilityVSEase of operation

Solution Approach 1:

The patent replaces the mechanical invasive biopsy procedure with a blood-based immunological assay measuring CD4+CD57+ T cells. This substitution maintains surveillance reliability by detecting early immune responses while eliminating the invasiveness and false-negative issues associated with transbronchial biopsies

Inventive Principle:

Principle #28Mechanics substitution (Replace mechanical system)

Data Source

PatentUS20230349902A1Novel t cells and the uses thereof

Publication Date: 2023.11.02 HOPITAL FOCH

AI summary

The invention relates to a new population of T cells, expressing the following biomarkers: CD3, CD4, CD57 and ILT2, as well to the uses thereof, such as for diagnosis, prognosis or treatment of various immune pathologies or responses, including graft rejection, autoimmune diseases, infectious diseases or cancers.