PD-L2 Biomarker Stratification for Esophagogastric Cancer Therapy

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Solution Overview

Problem

There is a pressing need for effective biomarkers to predict the response of esophagogastric cancers and metaplasias to PD-1 pathway inhibitors, as current treatments are minimally effective and lack reliable predictive tools.

Innovation Solution

The discovery of PD-L2 expression as a specific biomarker for predicting the response of esophagogastric cancers and metaplasias to PD-1 pathway inhibitors, involving methods to measure and compare PD-L2 expression levels in patient samples relative to control samples to determine likelihood of responsiveness.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If PD-1 pathway inhibitors are used to treat esophagogastric cancers, then treatment efficacy is improved for responsive patients, but the inability to predict response leads to ineffective treatment for non-responsive patients

Engineering Contradiction:

Improvetreatment efficacyVSAvoidresponse prediction information

Core Design Contradiction:

ReliabilityVSLoss of information

Solution Approach 1:

The patent applies preliminary action by measuring PD-L2 expression levels in tumor tissues before initiating PD-1 pathway inhibitor treatment. This pre-treatment biomarker assessment allows clinicians to predict which patients are likely to respond to immunotherapy, enabling informed treatment decisions before therapy begins. The method involves obtaining tissue samples, measuring PD-L2 expression using standardized protocols, and comparing results to established thresholds to determine treatment likelihood.

Inventive Principle:

Principle #10Preliminary action

2Adaptability or versatility

If molecularly targeted agents are used to treat esophagogastric cancers, then treatment specificity is improved, but the limited number of effective targets reduces overall treatment options

Engineering Contradiction:

Improvetreatment optionsVSAvoidnumber of effective targets

Core Design Contradiction:

Adaptability or versatilityVSQuantity of substance

Solution Approach 1:

The patent applies parameter changes by shifting from targeting a limited number of molecular markers (like HER2 in only 15% of patients) to measuring the expression level of PD-L2, a parameter that shows promise for predicting response in a broader population of esophagogastric cancer patients. This change in the measured parameter expands the potential pool of patients who can benefit from targeted immunotherapy.

Inventive Principle:

Principle #35Parameter changes

3Productivity

If cytotoxic chemotherapy is used as the primary treatment, then treatment applicability is maintained for all patients, but treatment effectiveness remains minimally beneficial

Engineering Contradiction:

Improvetreatment effectivenessVSAvoidtreatment applicability

Core Design Contradiction:

ProductivityVSEase of operation

Solution Approach 1:

The patent introduces PD-L2 expression measurement as an intermediary biomarker that connects the treatment decision to patient-specific characteristics. This intermediary allows the medical system to move from a one-size-fits-all chemotherapy approach to a personalized immunotherapy strategy, where the biomarker measurement mediates the selection of appropriate treatment based on individual patient tumor biology.

Inventive Principle:

Principle #24Intermediary (Mediator)

Data Source

PatentUS10948492B2PD-L2 biomarkers predictive of PD-1 pathway inhibitor responses in esophagogastric cancers

Publication Date: 2021.03.16 DANA FARBER CANCER INSTITUTE INC

AI summary

The present invention is based on the identification of novel biomarkers predictive of responsiveness of esophagogastric cancers to inhibitors of the PD-1 pathway.