WT1 Peptide Immunotherapy Prediction via IgG Subclass Titers

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Solution Overview

Problem

Current methods for predicting the clinical effect of WT1 peptide immunotherapy lack accuracy, making it difficult to determine the appropriateness of continued administration and assessing long-term treatment outcomes in patients with WT1-associated diseases.

Innovation Solution

A method involving the measurement of IgG antibody titers against WT1 antigen peptides, specifically using WT1 antigen peptides corresponding to the WT1 peptide vaccine, to assess the clinical effect by detecting binding and determining the subclasses IgG1, IgG3, and IgG4 levels, which correlates with overall survival and progression-free survival rates.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If conventional methods are used to predict clinical effect, then the prediction process is simple, but the accuracy of prediction is low

Engineering Contradiction:
Improveprediction accuracyVSAvoidmeasurement system complexity
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The patent segments the IgG antibody measurement into four distinct subclasses (IgG1, IgG2, IgG3, IgG4) and measures each separately. This segmentation allows for more precise prediction of clinical effect by capturing the nuanced immune response profile, where different subclasses contribute differently to therapeutic efficacy. The segmented measurement approach resolves the contradiction by sacrificing some system complexity to gain significant improvement in prediction accuracy.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The patent changes the measurement parameter from total IgG antibody level to specific IgG subclass titers (IgG1, IgG2, IgG3, IgG4). This parameter change enables more accurate prediction of clinical effect by detecting subtle variations in immune response that total IgG measurement cannot capture. The principle resolves the contradiction by transforming a simple measurement into a multi-parameter analysis that provides superior predictive accuracy.

Inventive Principle:
Principle #35Parameter changes

2Measurement precision

If IgG antibody titer measurement is performed to predict clinical effect, then prediction accuracy improves, but the measurement time and complexity increase

Engineering Contradiction:
Improveclinical effect prediction accuracyVSAvoidmeasurement time
Core Design Contradiction:
Measurement precisionVSLoss of time

Solution Approach 1:

The patent performs preliminary classification of the immune response by measuring all four IgG subclasses at predetermined time points (e.g., 4 weeks, 8 weeks, 12 weeks post-vaccination). This preliminary action establishes a baseline immune profile that correlates with long-term clinical outcomes. By conducting the comprehensive measurement early in the treatment protocol, the patent avoids the need for prolonged monitoring, thus resolving the contradiction between measurement time and prediction accuracy.

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The patent establishes a feedback mechanism where the measured IgG subclass titers are correlated with clinical outcomes (overall survival rate, progression-free survival rate). This feedback loop validates the measurement approach and allows for optimized prediction without requiring continuous long-term monitoring. The feedback principle resolves the time-accuracy contradiction by demonstrating that a single comprehensive measurement can predict long-term outcomes.

Inventive Principle:
Principle #23Feedback

3Measurement precision

If multiple IgG subclasses are measured separately, then prediction accuracy increases, but the ease of operation decreases

Engineering Contradiction:
Improveantibody titer measurement accuracyVSAvoidmeasurement procedure simplicity
Core Design Contradiction:
Measurement precisionVSEase of operation

Solution Approach 1:

The patent employs a universal measurement platform that can simultaneously or sequentially measure all four IgG subclasses using standardized ELISA protocols. This multi-functional approach maintains operational simplicity while achieving precise measurement of each subclass. The universal platform resolves the contradiction by allowing the same basic methodology to be applied across different measurements, reducing the operational burden despite the increased measurement scope.

Inventive Principle:
Principle #6Universality (Multi-functionality)

Solution Approach 2:

The patent uses identical ELISA measurement protocols for each IgG subclass, essentially creating copies of the same measurement process adapted for different antibody subclasses. This copying approach maintains ease of operation by repeating a proven, standardized procedure rather than developing complex new methods for each subclass. The principle resolves the contradiction by leveraging the simplicity of a single well-established method applied multiple times.

Inventive Principle:
Principle #26Copying

Applied Scientific Principles

This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.

Function Achieved in This Case

This approach provides a more accurate prediction of clinical effects, allowing for better judgment on the continuation of WT1 peptide vaccine administration and improving treatment outcomes by measuring anti-WT1 antigen peptide IgG antibody titers at specific time points post-administration.

Implementation Method 1

contacting a sample from the subject who has been given a WT1 peptide vaccine with a WT1 antigen peptide... and detecting the binding of the sample to the WT1 antigen peptide

Methodology Applied
Scientific EffectAntigen-antibody binding:

Data Source

PatentEP2998740B1Method for predicting clinical effect of immunotherapy
Publication Date: 2023.07.05 INT INST OF CANCER IMMUNOLOGY INC
  • EP2998740B1 patent drawingFigure 1
  • EP2998740B1 patent drawingFigure 2
  • EP2998740B1 patent drawingFigure 3

AI summary

Provided is a method for predicting a clinical effect on a subject in a WT1 peptide immunotherapy, said method comprising: a) a step for contacting a sample derived from the subject with WT1 antigen peptide or a variant thereof; and b) a step for detecting the binding of the sample to the WT1 antigen peptide or a variant thereof and thus measuring anti-WT1 antigen peptide IgG antibody titer existing in the sample, characterized in that an increase in the anti-WT1 antigen peptide IgG antibody titer in the subject determines the achievement of a favorable clinical effect. Also provided is a kit for performing the method according to the present invention, said kit containing WT1 antigen peptide or a variant thereof.