Multi-Antigen CAR T-Cells to Prevent AML Antigen Escape

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Solution Overview

Problem

Current treatment strategies for acute myeloid leukemia (AML) are inadequate, with high relapse rates and complications from conventional chemotherapy, and CAR T-cell therapies targeting single antigens face challenges in clinical translation and antigen escape.

Innovation Solution

Development of CAR-expressing cells that target multiple antigens, including CD33, CLL-1, CD123, and FLT3, using domain antibody (dAb) antigen binding domains to enhance cytotoxicity and reduce antigen escape.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Adaptability or versatility

If CAR T-cell therapy targets single antigen, then treatment simplicity is maintained, but antigen escape and relapse occur

Engineering Contradiction:

Improveantigen targeting coverageVSAvoidCAR structure complexity

Core Design Contradiction:

Adaptability or versatilityVSDevice complexity

Solution Approach 1:

The patent combines multiple antigen recognition domains (anti-CD33, anti-CLL-1, anti-CD123, anti-FLT3) into a single CAR T-cell construct, enabling simultaneous targeting of multiple AML antigens while maintaining a unified cellular therapy platform

Inventive Principle:

Principle #5Merging (Combining)

Solution Approach 2:

The CAR T-cells are designed with multi-antigen recognition capability, making them universally effective against diverse AML subtypes that express different antigen combinations, thereby achieving broad-spectrum coverage against AML

Inventive Principle:

Principle #6Universality (Multi-functionality)

2Reliability

If multi-antigen targeting is implemented, then antigen escape is reduced, but CAR structure and manufacturing complexity increase

Engineering Contradiction:

Improvetreatment efficacyVSAvoidCAR structure complexity

Core Design Contradiction:

ReliabilityVSDevice complexity

Solution Approach 1:

Multiple antigen-specific binding domains are merged into a single CAR molecule or co-expressed in the same T-cell, ensuring that the cell can recognize and eliminate target cells expressing any of the multiple antigens, thereby preventing antigen escape

Inventive Principle:

Principle #5Merging (Combining)

Solution Approach 2:

The CAR construct employs composite structure combining multiple antibody-derived binding domains (anti-CD33, anti-CLL-1, anti-CD123, anti-FLT3) with T-cell activating domains, creating a multi-functional composite receptor that enhances treatment reliability

Inventive Principle:

Principle #40Composite materials

3Productivity

If conventional chemotherapy is used, then initial remission is achieved, but relapse and complications occur

Engineering Contradiction:

Improveremission rateVSAvoidchemotherapy complications

Core Design Contradiction:

ProductivityVSObject-affected harmful factors

Solution Approach 1:

The patent replaces conventional chemotherapy (chemical system) with CAR T-cell immunotherapy (biological system), which provides sustained antileukemic activity through living cells that can proliferate and persist in the patient, avoiding chemotherapy-related complications

Inventive Principle:

Principle #28Mechanics substitution (Replace mechanical system)

Solution Approach 2:

The CAR T-cells are engineered to self-proliterate and self-persist in the patient's body, providing long-term immune surveillance and eliminating the need for repeated chemotherapy administrations, thereby reducing cumulative toxicity

Inventive Principle:

Principle #25Self-service

Data Source

PatentUS20250381224A1Car t-cells comprising an anti CD33, an anti CLL1 and at least one further car anti CD123 and/or ftl3

Publication Date: 2025.12.18 AUTOLUS LIMIED

AI summary

The present disclosure provides a cell comprising: an anti-CD33 chimeric antigen receptor (CAR); an anti-CLL 1 CAR; and an anti-CD123 and/or anti-CAR FLT3 CAR. The cell can be used in the treatment of a disease such as acute myeloid leukemia (AML).