Dual-Target CD19/22 CAR T-Cells for Antigen Escape in B-ALL

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Solution Overview

Problem

Current immunotherapeutic agents targeting CD19 antigen in pediatric B-cell acute lymphoblastic leukemia (B-ALL) face challenges such as antigen mutation leading to CD19-negative relapse and suboptimal synapse formation due to bulky antigens like CD22, which results in poor persistence and efficacy of CAR T-cell therapies.

Innovation Solution

Development of dual-targeting CD19/22 CAR T-cells expressing chimeric antigen receptors with CD19 and CD22-binding domains, utilizing a CD8 stalk spacer and intracellular signaling domains like 41BB and CD3-Zeta, to enhance synapse formation and persistence, thereby improving treatment efficacy for high-risk or relapsed B-ALL.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If single-antigen targeting (CD19) is used in CAR T-cell therapy, then initial treatment response is achieved, but antigen mutation leads to CD19-negative relapse

Engineering Contradiction:

Improvetreatment durabilityVSAvoidantigen escape capability

Core Design Contradiction:

ReliabilityVSAdaptability or versatility

Solution Approach 1:

The patent applies multi-functionality by engineering CAR T-cells to target multiple antigens (CD19 and CD22) simultaneously. This is achieved by co-expressing two different CAR receptors in the same T-cell population, enabling the therapy to recognize and eliminate leukemia cells expressing either antigen, thereby preventing antigen escape and improving treatment durability

Inventive Principle:

Principle #6Universality (Multi-functionality)

Solution Approach 2:

The patent creates a composite CAR T-cell product combining two distinct chimeric antigen receptors with different specificities (CD19-CAR and CD22-CAR). This composite approach integrates multiple functional elements within a single cellular therapy product, allowing simultaneous targeting of multiple antigens to prevent relapse

Inventive Principle:

Principle #40Composite materials

2Adaptability or versatility

If bulky antigens like CD22 are targeted, then additional antigen coverage is provided, but suboptimal synapse formation reduces CAR T-cell efficacy

Engineering Contradiction:

Improveantigen coverageVSAvoidsynapse formation efficiency

Core Design Contradiction:

Adaptability or versatilityVSReliability

Solution Approach 1:

The patent uses an optimized spacer region as an intermediary element between the antigen-binding domain and the signaling domain of the CAR receptor. This spacer acts as a mediator that improves the geometric arrangement for synapse formation, enabling effective signaling even when targeting bulky antigens like CD22, thus maintaining T-cell activation and killing efficiency

Inventive Principle:

Principle #24Intermediary (Mediator)

3Productivity

If intensive chemotherapy is administered to relapsed patients, then disease control is attempted, but poor outcomes occur due to maximal tolerable dose limits

Engineering Contradiction:

Improvedisease control efficacyVSAvoidtoxicity accumulation

Core Design Contradiction:

ProductivityVSObject-affected harmful factors

Solution Approach 1:

The patent replaces the mechanical/chemical system of intensive chemotherapy with a biological immunotherapeutic system (CAR T-cell therapy). This substitution leverages the patient's own immune system to recognize and eliminate leukemia cells, providing a novel mechanism of action that is not limited by chemotherapy dose constraints and toxicities

Inventive Principle:

Principle #28Mechanics substitution (Replace mechanical system)

Data Source

PatentUS20260097122A1CD19/c22 car t-cell treatment of high risk or relapsed pediatric acute lymphoblastic leukemia

Publication Date: 2026.04.09 AUTOLUS LIMIED

AI summary

The present disclosure relates to CD19/22 CAR T-cell products and methods for treating high risk or relapsed CD19+ or CD22+ haematological malignancies.