Targeting Pathogenic Immune Cells in Checkpoint Inhibitor Myocarditis

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Solution Overview

Problem

Current treatments for immune-related adverse events (irAE) such as ICI-induced myocarditis are limited, with glucocorticoids causing nonspecific side effects and a lack of personalized biomarkers for diagnosis and treatment.

Innovation Solution

The use of CCR1, CCR3, and CCR5 antagonists, along with anti-CD45RA antibodies, to target specific immune cells involved in ICI-induced myocarditis, thereby reducing immune-related adverse events.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If glucocorticoids are used to treat ICI-induced myocarditis, then immune-related adverse events are reduced, but nonspecific side effects occur and cardiac morbidity increases

Engineering Contradiction:

Improveeffectiveness in reducing immune-related adverse eventsVSAvoidnonspecific side effects and cardiac morbidity

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent applies local quality by targeting specific immune cell subsets (Temra CD8+ cells and monocytes/macrophages) with specific markers (CD45RA, CCR1, CCR3, CCR5) rather than using broad non-specific immunosuppression. This selective targeting allows treatment of myocarditis while preserving other immune functions and reducing nonspecific side effects.

Inventive Principle:

Principle #3Local quality

Solution Approach 2:

The patent segments the immune system into specific functional subsets involved in myocarditis pathogenesis (Temra CD8+ cytotoxic T cells and monocyte/macrophage populations) and addresses each subset separately with targeted therapies, rather than treating the immune system as a homogeneous whole.

Inventive Principle:

Principle #1Segmentation

2Reliability

If broad immunosuppressive treatment is used, then immune-related adverse events are treated, but immune cell selectivity is lost and specific mechanisms are not addressed

Engineering Contradiction:

Improvetreatment effectivenessVSAvoidimmune cell selectivity

Core Design Contradiction:

ReliabilityVSAdaptability or versatility

Solution Approach 1:

The patent identifies and targets specific local populations of immune cells (Temra CD8+ cells expressing cytotoxic markers and monocytes/macrophages with specific chemokine receptors) that are responsible for myocarditis pathogenesis, rather than applying uniform immunosuppression to all immune cells.

Inventive Principle:

Principle #3Local quality

Solution Approach 2:

The patent extracts and isolates the specific harmful immune cell subsets (Temra CD8+ cells and CCR2/CCR5+ monocytes/macrophages) from the broader immune system and targets them specifically, separating the pathogenic function from the protective immune functions.

Inventive Principle:

Principle #2Taking out (Extraction)

3Measurement precision

If personalized biomarkers are developed, then diagnosis precision is improved, but current lack of comprehensive human immune phenotyping data limits progress

Engineering Contradiction:

Improvediagnosis precisionVSAvoidcomprehensive human immune phenotyping data

Core Design Contradiction:

Measurement precisionVSLoss of information

Solution Approach 1:

The patent performs preliminary immune phenotyping of human subjects to identify and characterize Temra CD8+ cells and monocyte/macrophage subsets before myocarditis occurs, establishing baseline markers and molecular signatures that can be used for early diagnosis and monitoring.

Inventive Principle:

Principle #10Preliminary action

Solution Approach 2:

The patent uses flow cytometry and mass cytometry as intermediary technologies to bridge the gap between basic immune biology and clinical application, enabling comprehensive phenotyping of human immune cells and identification of diagnostic biomarkers.

Inventive Principle:

Principle #24Intermediary (Mediator)

Data Source

PatentUS20250026848A1Identification of pathogenic immune cell subsets in checkpoint inhibitor-induced myocarditis

Publication Date: 2025.01.23 THE BOARD OF TRUSTEES OF THE LELAND STANFORD JUNIOR UNIV

AI summary

This disclosure relates to methods helpful in diagnosing and treating immune check point inhibitor (ICI)-induced myocarditis as well as to using C-C chemokine receptor type 1 (CCR1), C-C chemokine receptor type 2 (CCR2), C-C chemokine receptor type 3 (CCR3) and C-C chemokine receptor type 5 (CCR5) antagonists and anti-CD45RA antibodies for treating ICI-induced myocarditis.