CAR-T Cells Targeting IL-1RAP for AML Treatment
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current treatments for acute myeloid leukemia (AML), particularly relapsed cases, face challenges with clinical toxicity and lack of efficacy, and there is a need for new therapies with acceptable toxicity profiles, as existing standard care options are ineffective in achieving long-term survival, especially for older patients.
Innovation Solution
Development of genetically modified T cells expressing a chimeric antigen receptor (CAR) targeting IL-1RAP, which includes an anti-IL-1RAP binding domain, a transmembrane domain, and an intracellular signaling domain, allowing for specific recognition and targeting of IL-1RAP-expressing leukemia cells.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If standard chemotherapy or radiation is used for AML treatment, then initial remission can be achieved, but long-term survival is limited and disease relapse occurs with increasing resistance
Solution Approach 1:
The patent uses CAR-T cells as an intermediary therapeutic agent that specifically targets IL-1RAP on AML cells. The CAR-T cells act as a mediator between the immune system and the leukemia cells, providing a mechanism to overcome chemotherapy resistance and achieve durable remission without the broad toxicity of standard treatments
Solution Approach 2:
The invention changes the therapeutic parameter from non-specific chemotherapy to highly specific CAR-T cell therapy targeting IL-1RAP. This parameter change enables selective destruction of AML cells while preserving normal hematopoietic cells, thereby improving long-term survival and reducing therapy resistance
2Reliability
If allogeneic stem cell transplantation is performed in second remission, then long-term survival chance is offered, but the procedure cannot be tolerated by most relapsed AML patients
Solution Approach 1:
The patent employs autologous CAR-T cells that can be generated from the patient's own T cells, avoiding the need for allogeneic stem cell transplantation. This approach provides a less toxic, more accessible therapy that does not require the patient to undergo intensive conditioning regimens, making it suitable for patients who cannot tolerate standard transplantation
3Reliability
If existing novel approaches like CAR-T cells targeting other antigens are used, then treatment efficacy is improved, but clinical toxicity limits their application
Solution Approach 1:
The patent applies local quality by selecting IL-1RAP as a tumor-associated antigen that is preferentially expressed on AML cells compared to normal cells. This localized expression pattern enables the CAR-T cells to exert their cytotoxic effect primarily on the leukemia cells, improving treatment efficacy while minimizing clinical toxicity to healthy tissues
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 CAR-T cells effectively target and kill IL-1RAP-expressing AML cells, demonstrating potential for improved treatment outcomes with minimal toxicity to healthy hematopoietic cells, offering a promising approach for relapsed AML patients, including those who cannot tolerate standard therapies.
Implementation Method 1
the CAR comprises an antibody or antibody fragment which includes an anti-IL-1RAP binding domain
Implementation Method 2
The CAR-T cells effectively target and kill IL-1RAP-expressing AML cells
Data Source
AI summary
The present invention is relative to a cell comprising a nucleic acid molecule encoding a chimeric antigen receptor (CAR) for use in the treatment of acute myeloid leukemia (AML), wherein the CAR comprises an antibody or antibody fragment which includes an anti-IL-1RAP binding domain, a transmembrane domain, and an intracellular signaling domain comprising at least a stimulatory domain