CD64 CAR T Cells for Venetoclax-Resistant AML Relapse

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Solution Overview

Problem

Existing treatments with venetoclax and azacitidine fail to achieve complete remission in approximately 30% of acute myeloid leukemia patients, and those who do achieve remission often relapse, necessitating alternative therapies for AML, particularly targeting leukemia stem cells.

Innovation Solution

Genetically modified immune cells, such as T cells, engineered to express chimeric antigen receptors (CARs) that bind to CD64, providing enhanced antigen-specific cytotoxicity and persistence, especially against CD64+ AML cells.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If venetoclax and azacitidine treatment is administered, then complete remission is achieved in 70% of patients, but 30% of patients do not respond and relapse occurs

Engineering Contradiction:

Improvetreatment efficacyVSAvoidresponse to alternative therapies

Core Design Contradiction:

ReliabilityVSAdaptability or versatility

Solution Approach 1:

The patent segments the AML cell population by CD64 expression levels, identifying CD64+ AML cells as a distinct targetable subset. This segmentation allows for focused therapeutic intervention against the specific cell population that drives relapse and resistance, rather than treating AML as a homogeneous disease.

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

The patent introduces CAR T cells as an intermediary therapeutic agent that specifically targets CD64+ AML cells. These engineered immune cells act as a bridge between the patient's immune system and the resistant AML cells, providing a mechanism to eliminate cells that have become resistant to conventional venetoclax and azacitidine treatment.

Inventive Principle:

Principle #24Intermediary (Mediator)

2Reliability

If conventional chemotherapy is used, then treatment is effective for eligible patients, but it is too aggressive for elderly or unfit patients

Engineering Contradiction:

Improvetreatment effectivenessVSAvoidpatient eligibility

Core Design Contradiction:

ReliabilityVSEase of operation

Solution Approach 1:

The patent changes the therapeutic parameter from conventional chemotherapy to CAR T cell immunotherapy. This parameter change allows treatment of elderly or unfit patients who cannot tolerate aggressive chemotherapy, while maintaining effectiveness against AML cells through the CD64-targeted CAR T cell mechanism.

Inventive Principle:

Principle #35Parameter changes

3Duration of action of moving object

If ven/aza treatment is administered, then 70% of patients achieve complete remission, but majority of patients relapse within two years

Engineering Contradiction:

Improveremission durationVSAvoidlong-term remission

Core Design Contradiction:

Duration of action of moving objectVSReliability

Solution Approach 1:

The patent applies preliminary action by targeting and eliminating CD64+ AML cells and leukemia stem cells before they can cause relapse. By using CAR T cells to preemptively destroy the resistant cell population that would otherwise survive ven/aza treatment and drive recurrence, the therapy extends remission duration and improves long-term outcomes.

Inventive Principle:

Principle #10Preliminary action

Data Source

PatentUS20260034217A1Compositions and methods for the treatment of ven/aza resistant acute myeloid leukemia

Publication Date: 2026.02.05 THE REGENTS OF THE UNIVERSITY OF COLORADO

AI summary

The disclosure describes T cells that express chimeric antigen receptors (CARs), as well as pharmaceutical compositions comprising T cells and methods of making and using such T cells. Particularly, this disclosure describes T cells expressing a CAR that binds to CD64, and methods of use in treating acute myeloid leukemia.