Antigen Processing Gene Detection for Checkpoint Blockade Resistance

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Solution Overview

Problem

Current methods for identifying mechanisms of resistance to checkpoint blockade (CPB) therapy in cancer patients are inadequate, limiting the ability to optimally select patients for therapy and predict durable responses.

Innovation Solution

Detecting genetic modifications in genes related to antigen processing, such as the beta-2-microglobulin (B2M) gene, to identify cancer cells resistant to CPB therapy, allowing for alternative treatment approaches like NK cell therapy or gene therapy to restore function.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If comprehensive knowledge of resistance mechanisms is obtained, then treatment selection accuracy is improved, but diagnostic complexity and cost increase

Engineering Contradiction:

Improvetreatment selection accuracyVSAvoiddiagnostic complexity

Core Design Contradiction:

Measurement precisionVSDevice complexity

Solution Approach 1:

The patent extracts and focuses on a specific subset of resistance mechanisms (genetic modifications in antigen processing genes like B2M) rather than attempting to diagnose all possible resistance mechanisms. This selective approach maintains high diagnostic accuracy for the most clinically relevant resistance types while significantly reducing the complexity of the diagnostic system.

Inventive Principle:

Principle #2Taking out (Extraction)

Solution Approach 2:

The diagnostic method segments the complex problem of CPB resistance into distinct detectable components - specifically genetic modifications in antigen processing genes. By dividing the resistance mechanism into identifiable genetic markers, the system achieves precise treatment selection without requiring comprehensive analysis of all resistance pathways.

Inventive Principle:

Principle #1Segmentation

2Measurement precision

If genetic modifications in antigen processing genes are detected, then resistance identification accuracy is improved, but testing cost increases

Engineering Contradiction:

Improveresistance identification accuracyVSAvoidtesting cost

Core Design Contradiction:

Measurement precisionVSQuantity of substance

Solution Approach 1:

The patent changes the diagnostic parameter from comprehensive resistance profiling to specific detection of genetic modifications in antigen processing genes. This parameter change maintains high resistance identification accuracy for the most clinically relevant cases while reducing testing cost by focusing resources on the most impactful genetic markers rather than进行全面 screening.

Inventive Principle:

Principle #35Parameter changes

Data Source

PatentUS11634777B2Resistance to checkpoint blockade therapy

Publication Date: 2023.04.25 THE GENERAL HOSPITAL CORP

AI summary

Provided herein are methods of determining resistance to checkpoint blockade (CPB) therapy in a cancer patient, methods of typing tumor cells of a cancer patient, methods of assigning treatment to a cancer patient and methods of treatment of a cancer patient based on determining in a tumor sample of said patient, reduced expression of a gene relating to antigen processing pathway or a product thereof, or a modification causing said reduced expression, wherein the presence of said reduced expression or modification is indicative of resistance to CPB therapy.