Anti-CD33 CARs for AML Remission

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Solution Overview

Problem

Current treatment regimens for acute myelogenous leukemia (AML) in children and young adults have limited effectiveness, with only 60% achieving long-term remission, necessitating new therapeutic strategies to increase remission rates and improve overall survival.

Innovation Solution

Development of chimeric antigen receptors (CARs) specifically targeting CD33, comprising an antigen binding domain, a transmembrane domain, and an intracellular T cell signaling domain, which are used to redirect T-cell specificity and induce an immune response against AML cells.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If conventional chemotherapy and stem cell transplantation are used to treat AML, then some patients achieve remission, but the overall remission rate is limited to 60% and relapse occurs frequently

Engineering Contradiction:

Improveremission rateVSAvoidoverall survival

Core Design Contradiction:

ReliabilityVSProductivity

Solution Approach 1:

The patent introduces CAR-T cells as an intermediary therapeutic agent that bridges conventional chemotherapy and direct tumor cell elimination. The chimeric antigen receptors serve as mediators that redirect T-cell specificity toward CD33-positive AML cells, enabling a more effective immune response that overcomes the limitations of conventional therapy alone

Inventive Principle:

Principle #24Intermediary (Mediator)

Solution Approach 2:

The invention changes the fundamental parameter of immune cell specificity by engineering T cells with chimeric antigen receptors that recognize CD33. This parameter change transforms non-specific or weakly specific immune responses into highly specific anti-AML activity, thereby improving remission rates and reducing relapse

Inventive Principle:

Principle #35Parameter changes

2Reliability

If intensive multi-agent chemotherapy is administered to treat AML, then some therapeutic effect is achieved, but treatment effectiveness remains limited and toxicity increases

Engineering Contradiction:

Improvetreatment effectivenessVSAvoidtoxicity

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent extracts the essential anti-tumor function from complex multi-agent chemotherapy and concentrates it into a targeted immunotherapy approach. By isolating the CD33 antigen as the specific target and engineering T cells to recognize only this antigen, the therapy achieves treatment effectiveness while avoiding the diffuse toxicity of conventional chemotherapy

Inventive Principle:

Principle #2Taking out (Extraction)

Solution Approach 2:

The invention converts the harmful lack of specificity in conventional chemotherapy into a benefit by creating highly specific CAR-T cells that target only CD33-positive AML cells. This specificity transforms the previously harmful collateral damage to healthy cells into a precise therapeutic action that spares normal tissue

Inventive Principle:

Principle #22Blessing in disguise (Convert harm into benefit)

Data Source

PatentUS20210017277A1Anti-CD33 chimeric antigen receptors and their uses

Publication Date: 2021.01.21 THE GOVERNMENT OF THE UNITED STATES OF AMERICA AS REPRESENTED BY THE SECRETARY DEPARTMENT OF HEALTH & HUMAN SERVICES

AI summary

Embodiments of the invention provide chimeric antigen receptors (CARs) having antigenic specificity for CD33. Nucleic acids, recombinant expression vectors, host cells, populations of cells, and pharmaceutical compositions relating to the CARs are disclosed. Methods of detecting the presence of cancer in a mammal and methods of treating or preventing cancer in a mammal are also disclosed.