Modified Immune Cells Reduce Cytokine Toxicity

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Solution Overview

Problem

Adoptive cell transfer immunotherapy is limited by toxicity issues, such as cytokine-associated toxicity, which can be fatal due to systemic overproduction of inflammatory cytokines.

Innovation Solution

Development of immune cells with reduced inflammatory properties by knocking out inflammatory proteins and introducing cytokine antagonists, specifically targeting cytokines like IL-2, to mitigate cytokine-associated toxicity while maintaining therapeutic efficacy.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If immune cells are used in adoptive cell transfer therapy to target malignant cells, then therapeutic efficacy is improved, but cytokine-associated toxicity increases due to non-physiologic elevation of cytokine levels

Engineering Contradiction:

Improvetherapeutic efficacyVSAvoidcytokine-associated toxicity

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent extracts and removes the harmful inflammatory cytokine production capability from immune cells through genetic modification. Specifically, the immune cells are engineered to lack the ability to produce excessive inflammatory cytokines while retaining their antigen-specific recognition and cytotoxic functions, thereby separating the therapeutic function from the harmful side effect

Inventive Principle:

Principle #2Taking out (Extraction)

Solution Approach 2:

The patent converts the harmful cytokine storm response into a beneficial controlled immune response. By genetically modifying immune cells to produce reduced levels of inflammatory cytokines, the therapy maintains effective anti-tumor immunity while preventing the dangerous systemic inflammation that would otherwise occur

Inventive Principle:

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

2Strength

If immune cells produce high levels of inflammatory cytokines to enhance anti-tumor activity, then immune response strength is improved, but patient safety deteriorates due to potential death from cytokine release syndrome

Engineering Contradiction:

Improveimmune response strengthVSAvoidpatient safety

Core Design Contradiction:

StrengthVSReliability

Solution Approach 1:

The patent changes the quantitative parameter of cytokine production by the immune cells. Through genetic modification, the cells are engineered to produce reduced levels of inflammatory cytokines compared to wild-type cells, thereby adjusting the immune response to a safe yet effective range that prevents cytokine release syndrome while maintaining anti-tumor activity

Inventive Principle:

Principle #35Parameter changes

Data Source

PatentUS20240141292A1Modification of immune cells for reducing toxicity and uses thereof in adoptive cell therapy

Publication Date: 2024.05.02 HUNAN SIWEIKANG THERAPEUTICS CO LTD

AI summary

A population of immune cells comprising modified immune cells with reduced inflammatory properties, wherein such modified immune cells may have reduced production of one or more inflammatory cytokines (e.g., interleukin 2), and/or express one or more antagonists of one or more inflammatory cytokines (e.g., interleukin 6). Also provided herein are methods of producing such immune cell populations comprising the modified immune cells and methods of using such in cell therapy (e.g., to treat cancer, infectious diseases or immune diseases).