WT-1 Peptides Binding Multiple HLA Haplotypes

Resolve Bottlenecks,
Find Innovative SolutionsGenerate Solutions

Solution Overview

Problem

Current WT1-derived peptides for cancer therapy are limited to specific HLA haplotypes, such as HLA-A0201 and HLA-A2402, restricting their therapeutic application to only a portion of the global population, as they do not effectively stimulate T cells in individuals with other HLA haplotypes.

Innovation Solution

Development of novel peptides with amino acid sequences that bind to multiple HLA haplotypes, allowing them to stimulate T cells across a broader range of the population, including those with HLA-A0201 and HLA-A2402, and potentially other HLA haplotypes, for use in vaccines and immunotherapies targeting WT1-expressing cancers.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If peptides are designed to bind to specific HLA haplotypes (HLA-A0201, HLA-A2402), then strong T cell responses are induced in individuals with those haplotypes, but the therapeutic application is limited to only a portion of the global population

Engineering Contradiction:

ImproveT cell response strengthVSAvoidpopulation coverage

Core Design Contradiction:

ReliabilityVSAdaptability or versatility

Solution Approach 1:

The patent applies universality by designing peptides that can bind to multiple HLA haplotypes simultaneously. The identified peptides (e.g., SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4) are engineered with amino acid sequences that accommodate binding motifs for different HLA class I molecules, enabling a single peptide to serve multiple HLA types and thereby expand population coverage while maintaining immunogenicity

Inventive Principle:

Principle #6Universality (Multi-functionality)

Solution Approach 2:

The patent employs parameter changes by systematically modifying peptide amino acid sequences to optimize binding affinity across multiple HLA haplotypes. Through structural analysis and iterative design, the peptides' physical-chemical parameters (amino acid composition, binding groove compatibility) are adjusted to achieve broad HLA binding while preserving T cell epitope functionality

Inventive Principle:

Principle #35Parameter changes

2Adaptability or versatility

If peptides are designed to bind to multiple HLA haplotypes, then population coverage is expanded, but the strength and specificity of T cell responses may be reduced

Engineering Contradiction:

Improvepopulation coverageVSAvoidT cell response strength

Core Design Contradiction:

Adaptability or versatilityVSReliability

Solution Approach 1:

The patent applies local quality by identifying and preserving critical anchor residues and T cell contact residues within the peptide sequence. Specific amino acid positions are optimized for HLA binding while other positions are maintained for T cell recognition, ensuring that multi-HLA binding capability does not compromise immunogenicity. The peptide structure is locally optimized at key positions to maintain strong T cell responses across different HLA backgrounds

Inventive Principle:

Principle #3Local quality

Solution Approach 2:

The patent employs dynamics by creating peptides with flexible binding characteristics that can adapt to different HLA haplotype variations. The peptide sequences are designed with certain degrees of conformational flexibility and binding affinity modulation, allowing them to effectively bind to multiple HLA class I molecules with varying binding grooves while maintaining sufficient stability for immunogenic recognition

Inventive Principle:

Principle #15Dynamics

Data Source

PatentEP3769782A1Immunogenic WT-1 peptides and methods of use thereof

Publication Date: 2021.01.27 MEMORIAL SLOAN KETTERING CANCER CENT

Figure 1
Figure 2A~2B
Figure 3~4A

AI summary

This invention provides an isolated peptide comprising the amino acid sequence NYMNLGATL (SEQ ID NO:7) and uses thereof.