EMPD-Specific CAR for IgE-Mediated Allergic Disease Therapy

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Solution Overview

Problem

Current treatments for atopic diseases like allergic asthma are inadequate, particularly in suppressing IgE levels over a long period with a single treatment, as existing therapies require frequent administration and are costly, and do not effectively target IgE production.

Innovation Solution

Development of an EMPD-specific chimeric antigen receptor (CAR) comprising an extracellular ligand binding domain, a transmembrane domain, and an intracellular domain that mediates T cell activation upon binding to EMPD, specifically targeting and suppressing IgE-producing B cells by redirecting T cell responses.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If omalizumab is used to target IgE, then IgE levels are suppressed, but frequent administration is required and treatment costs are high

Engineering Contradiction:

ImproveIgE suppression effectivenessVSAvoidTreatment duration between administrations

Core Design Contradiction:

ReliabilityVSDuration of action of moving object

Solution Approach 1:

The patent applies preliminary action by genetically modifying T cells ex vivo to express CAR receptors that specifically target IgE-producing B cells. This preparatory modification allows the engineered T cells to persistently suppress IgE production in vivo over extended periods, eliminating the need for frequent re-administration of therapeutic agents while maintaining reliable IgE suppression.

Inventive Principle:

Principle #10Preliminary action

Solution Approach 2:

The engineered CAR T cells exhibit self-service characteristics by autonomously recognizing and eliminating IgE-producing B cells without requiring external re-administration. The modified T cells persist in the patient's body, continuously performing the therapeutic function of suppressing IgE production, thereby extending the duration of action and reducing treatment frequency.

Inventive Principle:

Principle #25Self-service

2Reliability

If omalizumab is used to target IgE, then IgE levels are suppressed, but treatment costs are high

Engineering Contradiction:

ImproveIgE suppression effectivenessVSAvoidTreatment cost

Core Design Contradiction:

ReliabilityVSEase of manufacture

Solution Approach 1:

The patent employs a one-time cellular therapy approach where engineered T cells are administered as a single dose that provides long-lasting or potentially permanent therapeutic effect. This replaces the recurring cost of expensive monoclonal antibody administrations with a single manufacturing and administration event, significantly reducing overall treatment costs while maintaining reliable IgE suppression.

Inventive Principle:

Principle #27Cheap short-living objects (Disposable)

3Reliability

If existing therapies are used, then IgE levels are suppressed, but IgE production is not effectively targeted

Engineering Contradiction:

ImproveIgE level suppressionVSAvoidTargeting specificity

Core Design Contradiction:

ReliabilityVSAdaptability or versatility

Solution Approach 1:

The patent applies local quality by engineering T cells with CAR receptors that specifically recognize and bind to IgE on the surface of IgE-producing B cells. This localized targeting mechanism directs the therapeutic action precisely at the source of IgE production (IgE+ B cells) rather than systemically suppressing all B cells or IgE in circulation, thereby achieving both effective IgE level suppression and high targeting specificity.

Inventive Principle:

Principle #3Local quality

Solution Approach 2:

The CAR-modified T cells serve as an intermediary between the immune system and IgE-producing B cells. The chimeric antigen receptor on the T cells acts as a mediator that specifically recognizes IgE on B cells and translates this recognition into targeted cytotoxic activity, enabling precise targeting of IgE production while maintaining effective suppression of IgE levels.

Inventive Principle:

Principle #24Intermediary (Mediator)

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

The EMPD-specific CAR provides long-term suppression of IgE production by specifically targeting and eliminating IgE-producing B cells, potentially offering a more effective and sustainable treatment for allergic diseases compared to existing therapies.

Implementation Method 1

an extracellular ligand binding domain capable of binding EMPD

Methodology Applied

Scientific EffectAntigen-antibody binding:

Implementation Method 2

an intracellular domain that mediates T cell activation upon binding of EMPD to the extracellular ligand binding domain

Methodology Applied

Scientific EffectSignal transduction:

Implementation Method 3

specifically targeting and suppressing IgE-producing B cells by redirecting T cell responses

Methodology Applied

Scientific EffectAdoptive T-cell therapy:

Data Source

PatentUS11384156B2Adoptive T-cell therapy using EMPD-specific chimeric antigen receptors for treating IgE-mediated allergic diseases

Publication Date: 2022.07.12 THE NEMOURS FOUND

AI summary

A chimeric antigen receptor specific for the extracellular membrane-proximal domain (EMPD) of membrane-bound IgE (mIgE) is provided. The EMPD-specific chimeric antigen receptor comprises an extracellular ligand binding domain capable of binding EMPD, a transmembrane domain, and an intracellular domain that mediates T cell activation upon EMPD binding. Nucleic acids and vectors encoding the EMPD-specific chimeric antigen receptor are provided. T cells transduced with such vectors find use in chimeric antigen receptor-based adoptive T-cell therapy for targeting IgE-expressing B cells and treating IgE-mediated allergic diseases.