WT1 Peptide Binding Multiple HLA Molecules for T Cell Activation

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Solution Overview

Problem

There is a need for a WT1 peptide that can bind to HLA-DRB1*1501, HLA-DPB1*0901, and HLA-DPB1*0501 molecules to effectively activate helper T cells for cancer treatment and prevention, as existing peptides only bind to specific subtypes like HLA-DRB1*0401, HLA-DRB1*0405, and HLA-DRB1*1502, and there is a lack of promiscuous peptides that can bind to multiple MHC class II molecules.

Innovation Solution

A WT1 peptide with the amino acid sequence Lys Arg Tyr Phe Lys Leu Ser His Leu Gln Met His Ser Arg Lys His is found to bind to HLA-DRB1*1501, HLA-DPB1*0901, and HLA-DPB1*0501 molecules, allowing for the activation of helper T cells by being added to antigen-presenting cells, and can also bind to HLA-DRB1*0405 and HLA-DRB1*1502 molecules.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Adaptability or versatility

If existing WT1 peptides are used to activate helper T cells, then helper T cell activation is achieved for specific MHC class II subtypes, but the applicability is limited to narrow populations with specific HLA types

Engineering Contradiction:

Improveapplicability to different MHC class II moleculesVSAvoideffectiveness of helper T cell activation

Core Design Contradiction:

Adaptability or versatilityVSReliability

Solution Approach 1:

The patent identifies WT1 peptide sequences that can bind to multiple MHC class II molecules including HLA-DRB1*1501, HLA-DPB1*0901, and HLA-DPB1*0501. This multi-binding capability allows a single peptide to activate helper T cells across diverse human populations, transforming a subtype-specific solution into a universal one that covers approximately 90% of the Japanese population and broader global applicability.

Inventive Principle:

Principle #6Universality (Multi-functionality)

2Adaptability or versatility

If promiscuous helper peptides binding to multiple MHC class II molecules are developed, then the coverage of human populations is expanded, but the identification and development becomes extremely difficult

Engineering Contradiction:

Improvecoverage of MHC class II subclassesVSAvoiddifficulty of identifying promiscuous peptides

Core Design Contradiction:

Adaptability or versatilityVSDevice complexity

Solution Approach 1:

The patent employs systematic screening of WT1 peptide sequences with varying amino acid compositions to identify those with promiscuous binding capabilities. By changing peptide parameters (amino acid sequence, length, composition) and testing binding affinity across multiple MHC class II molecules, the researchers successfully identified sequences like those binding to HLA-DRB1*1501, HLA-DPB1*0901, and HLA-DPB1*0501, overcoming the complexity through methodical parameter optimization.

Inventive Principle:

Principle #35Parameter changes

3Reliability

If helper T cell activation is enhanced through MHC class II-binding peptides, then cancer immunotherapy effectiveness is increased, but the benefit is limited to patients with specific HLA types

Engineering Contradiction:

Improveeffectiveness of cancer immunotherapyVSAvoidapplicability across different patient populations

Core Design Contradiction:

ReliabilityVSAdaptability or versatility

Solution Approach 1:

The patent develops WT1-based cancer vaccines containing peptide sequences that bind to multiple MHC class II molecules (HLA-DRB1*1501, HLA-DPB1*0901, HLA-DPB1*0501). This universal binding capability ensures that patients across different HLA types can mount effective helper T cell responses, thereby enhancing cancer immunotherapy effectiveness across diverse populations rather than being restricted to specific HLA-matched groups.

Inventive Principle:

Principle #6Universality (Multi-functionality)

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 peptide enables the activation of helper T cells in a wide range of subjects with different MHC class II molecules, providing a method for treating and preventing cancer by activating immune systems in vivo and in vitro, covering about 90% of Japanese population's MHC class II subclasses.

Implementation Method 1

the WT1 peptide has an ability to bind to an HLA-DRB1*1501 molecule, an HLA-DPB1*0901 molecule or an HLA-DPB1*0501 molecule

Methodology Applied

Scientific EffectMolecular binding: Chemical Bonding

Data Source

PatentUS11555814B2Method for activation of helper t cell and composition for use in the method

Publication Date: 2023.01.17 INT INST OF CANCER IMMUNOLOGY INC

AI summary

Disclosed are: a method for activating a helper T cell, which comprises the step of adding a WT1 peptide to an antigen-presenting cell to activate the helper T cell, wherein the WT1 peptide is capable of binding to any one selected from an HLA-DRB1*1501 molecule, an HLA-DPB1*0901 molecule and an HLA-DPB1*0501 molecule; a composition for use in the method; a therapeutic and/or prophylactic method for cancer by activating a helper T cell; a pharmaceutical composition for use in the therapeutic and/or prophylactic method; and others.