WT-1 Peptides for Broad HLA Binding
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Solution Overview
Problem
Current WT1-derived peptides for cancer immunotherapy are limited to specific HLA haplotypes, restricting their therapeutic application to only 40% of Caucasians and 40% of Japanese and other Asian populations, necessitating the development of peptides that can bind to multiple HLA haplotypes to broaden their therapeutic potential.
Innovation Solution
Development of novel WT1-derived peptides with specific amino acid sequences that can bind to multiple HLA class I and II haplotypes, allowing for the stimulation of T cells across a broader population, which can then be used in vaccines or administered to patients for treatment.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If WT1-derived peptides are designed to bind to specific HLA haplotypes (e.g., HLA-A0201 or HLA-A2402), then strong immune responses are induced in those specific populations, but the therapeutic application is limited to only 40% of Caucasians and 40% of Japanese and other Asian populations
Solution Approach 1:
The patent designs WT1-derived peptides that can bind to multiple HLA haplotypes simultaneously, making a single peptide formulation universally applicable to diverse populations. The peptides are engineered with specific amino acid sequences that accommodate binding motifs for different HLA class I and class II molecules, thereby achieving multi-functionality across various genetic backgrounds without requiring population-specific formulations.
Solution Approach 2:
The patent employs parameter changes by modifying amino acid sequences at specific positions within the peptide to create binding compatibility with multiple HLA haplotypes. By altering key anchor residues and optimizing the peptide sequence, the invention achieves broader HLA binding specificity while maintaining immunogenicity, thus expanding population coverage from 40% to potentially 80-90% of the global population.
2Adaptability or versatility
If multiple WT1-derived peptides targeting different HLA haplotypes are developed, then broader population coverage is achieved, but the complexity of vaccine formulation and administration increases
Solution Approach 1:
The patent merges multiple peptide sequences into a single multi-component vaccine formulation that targets multiple HLA haplotypes simultaneously. Instead of requiring separate vaccines for different populations, the invention combines peptides with complementary HLA binding specificities into one formulation, thereby achieving broad population coverage while simplifying administration to a single unified vaccine product.
Solution Approach 2:
The patent segments the vaccine formulation into distinct peptide components, each optimized for binding to specific HLA haplotypes. This segmentation allows for modular design where individual peptide sequences can be independently optimized for specific HLA bindings, yet remain part of a cohesive multi-component formulation that collectively covers diverse populations.
Data Source
AI summary
This invention provides peptides, immunogenic compositions and vaccines, and methods of treating, reducing the incidence of, and inducing immune responses to a WT1-expressing cancer, comprising heteroclitic peptides derived from the WT-1 protein.