IL-10 and IL-4 Modulation of CAR-T Cytokine Release Syndrome

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Solution Overview

Problem

Cytokine Release Syndrome (CRS) is a dose and treatment-related toxicity resulting from Bispecific T cell Engager (BiTE) and Chimeric Antigen Receptor T cell (CAR-T) therapies, characterized by uncontrolled induction of proinflammatory cytokines like IL-6, IL-1β, TNFα, and IFNγ, with the molecular circuit responsible for induction unknown.

Innovation Solution

Treatment of monocytes with IL-10, IL-4, IL-12, IL-15, IL-7, or their half-life extended versions, or diakines comprising these cytokines, to inhibit the induction of proinflammatory cytokines and reduce CRS.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If BiTE or CAR-T therapy is administered to activate T cells for tumor cell cytolysis, then anti-tumor efficacy is improved, but cytokine release syndrome (CRS) occurs due to uncontrolled induction of proinflammatory cytokines

Engineering Contradiction:

Improveanti-tumor efficacyVSAvoidcytokine release syndrome

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent introduces IL-10 or IL-4 as intermediary cytokines that mediate between the T cell activation and the proinflammatory cytokine induction. These intermediary cytokines bind to specific receptors on monocytes and directly inhibit the induction of proinflammatory cytokines by IL-2, thereby reducing CRS while preserving anti-tumor efficacy

Inventive Principle:

Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent applies preliminary anti-action by administering IL-10 or IL-4 before or concurrently with BiTE/CAR-T therapy to preemptively block the molecular circuit that leads to CRS. By treating monocytes with these cytokines in advance, the patent prevents the uncontrolled induction of proinflammatory cytokines before CRS can develop

Inventive Principle:

Principle #9Preliminary anti-action

2Productivity

If high levels of proinflammatory cytokines are induced to enhance immune response, then tumor cell cytolysis is improved, but toxic side effects increase

Engineering Contradiction:

Improvetumor cell cytolysisVSAvoidtoxic side effects

Core Design Contradiction:

ProductivityVSObject-generated harmful factors

Solution Approach 1:

The patent applies local quality by selectively modulating cytokine induction in specific cell types (monocytes) rather than globally suppressing all immune responses. IL-10 or IL-4 treatment specifically targets monocyte-derived proinflammatory cytokines while preserving T cell-mediated tumor cell cytolysis, achieving localized control of harmful effects

Inventive Principle:

Principle #3Local quality

Solution Approach 2:

The patent converts the harmful effect of IL-2-induced proinflammatory cytokine induction into a benefit by using IL-10 or IL-4 to selectively block only the toxic pathway. The IL-2 continues to drive anti-tumor immunity through T cells, while the harmful monocyte-derived cytokines are inhibited, transforming a harmful side effect into a controlled therapeutic outcome

Inventive Principle:

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

Data Source

PatentUS12552849B2Method of reducing bispecific t cell engager or chimeric antigen receptor t cell mediated cytokine release syndrome using interleukins-4, -10, or a fusion protein thereof

Publication Date: 2026.02.17 DEKA BIOSCIENCES INC

AI summary

The disclosure provides for various methods including a method of reducing the severity of bispecific T cell engager (BiTE) or chimeric antigen receptor T cell (CAR-T) induced cytokine release syndrome (CRS) comprising administering to a patient in need thereof an amount of a composition comprising an interleukin 10 (IL-10) or an IL-10 agent, an interleukin 4 (IL-4) or an IL-4 agent, or combinations thereof.