Macrophage CAR Therapy Avoiding Cytokine Storms

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Solution Overview

Problem

Current cancer therapies face challenges in effectively targeting and eliminating cancer cells due to the immune system's response to cancer antigens, particularly the risk of cytokine storms and long-term activation of modified T-cells, which can lead to harmful immune responses.

Innovation Solution

Modifying macrophages to create Macrophage Chimeric Antigen Receptor (MOTO-CAR) cells that target cancer-specific antigens like Thymidine Kinase 1 (TK1) and Hypoxanthine-Guanine Phosphoribosyltransferase (HPRT), which are exclusively expressed on cancer cells, to induce a localized M1 response without the risks associated with T-cell CAR therapies.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If T-cells are modified with chimeric antigen receptors to target cancer antigens, then cancer cell targeting capability is improved, but risk of cytokine storms and long-term immune activation increases

Engineering Contradiction:

Improvecancer cell targeting capabilityVSAvoidcytokine storms and long-term immune activation

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent inverts the conventional approach by using macrophages instead of T-cells as the carrier for chimeric antigen receptors. This inversion allows the same cancer-targeting function to be achieved while avoiding the harmful cytokine storm responses typically associated with CAR-T cell therapy, as macrophages have different activation profiles and safety profiles

Inventive Principle:

Principle #13The other way round (Inversion)

Solution Approach 2:

The patent creates a functional copy of the cancer-targeting mechanism by transferring the antigen recognition capability (via scFv) to macrophages through chimeric antigen receptors. This copying allows the anti-tumor function to be replicated in a different cell type that does not carry the same risks as T-cells

Inventive Principle:

Principle #26Copying

2Productivity

If macrophages are modified with chimeric antigen receptors to target cancer antigens, then cancer treatment efficacy is improved, but complexity of immune cell modification increases

Engineering Contradiction:

Improvecancer treatment efficacyVSAvoidcomplexity of immune cell modification

Core Design Contradiction:

ProductivityVSDevice complexity

Solution Approach 1:

The patent employs universal components for macrophage modification, including standardized scFv fragments from anti-cancer antibodies and common signaling domains (such as CD3ζ and co-stimulatory domains), which can be applied across different cancer targets and macrophage subsets, thereby reducing overall modification complexity despite the novel approach

Inventive Principle:

Principle #6Universality (Multi-functionality)

Data Source

PatentUS20220372170A1Macrophage CAR (MOTO-CAR) In Immunotherapy

Publication Date: 2022.11.24 ONEILL KIM LESLIE

AI summary

Modified macrophage immune cells are provided for treatment of cancer and other diseases. In particular said macrophages express chimeric antigen receptors (CAR). The single chain variable fragment (scFv) may be directed against thymidine kinase 1 (TK1) or hypoxanthine guanine phosphoribosyltransferase (HPRT). The signaling domain may be derived from a Toll-like receptor (TLR).