Multi-Antigen CAR Cell Targeting for AML With Lower Off-Tumor Toxicity
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Solution Overview
Problem
Current CAR therapies for AML lack suitable targets that are highly expressed in leukemia cells but minimally expressed in normal tissues, leading to potential toxicity and limited efficacy due to 'on-target, off-tumor' effects.
Innovation Solution
Engineering immunoresponsive cells, such as T cells, to express a combination of antigen recognizing receptors (CARs and TCRs) that target multiple antigens like EMR2, CD33, and others, with specific binding affinities and co-stimulatory receptors to enhance activation and minimize toxicity.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If CAR therapy targets are selected based on high expression in cancer cells, then tumor targeting efficacy is improved, but toxicity to normal tissues increases due to expression of same targets on normal cells
Solution Approach 1:
The patent segments the targeting approach by using multiple distinct CAR targets (CD33, CD123, CD70, CD96) rather than relying on a single target. This segmentation allows the system to distribute the targeting function across multiple antigens, reducing the burden on any single target and thereby minimizing off-tumor toxicity while maintaining comprehensive tumor coverage.
Solution Approach 2:
The patent implements multi-functionality by designing CAR T cells to recognize multiple different antigens (CD33, CD123, CD70, CD96) simultaneously. This universal approach enables a single CAR T cell product to target various tumor antigens, ensuring broad tumor coverage while selecting targets that are minimally expressed on normal tissues to reduce toxicity.
2Productivity
If conventional CAR therapy is used for AML, then treatment simplicity is maintained, but therapeutic efficacy is insufficient due to lack of suitable targets and on-target off-tumor effects
Solution Approach 1:
The patent merges multiple CAR targeting capabilities into a single integrated therapy product. By combining CARs against CD33, CD123, CD70, and CD96 into one treatment formulation, the system achieves enhanced therapeutic efficacy through multi-antigen targeting while presenting a unified treatment approach rather than requiring multiple separate therapies.
Data Source
AI summary
The presently disclosed subject matter provides methods and compositions for treating myeloid disorders (e.g., acute myeloid leukemia (AML)). It relates to immunoresponsive cells bearing antigen recognizing receptors (e.g., chimeric antigen receptors (CARs)) targeting AML-specific antigens.