Mutated WT1 Peptides for HLA Binding and T Cell Activation
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current treatments for Wilms tumor (WT), a pediatric nephroblastoma, do not effectively address the genetic alterations leading to WT1-expressing cancers, limiting the induction of specific immune responses and treatment efficacy.
Innovation Solution
Development of immunogenic peptides and compositions, including mutated WT1 peptides with specific binding motifs for HLA Class I and II molecules, designed to induce immune responses by stimulating CD8+ and CD4+ lymphocytes, thereby targeting WT1-expressing cancers.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional treatments are used for Wilms tumor, then treatment can be administered, but specific immune responses are not effectively induced
Solution Approach 1:
The patent applies parameter changes by modifying the amino acid sequence of WT1 peptides to create mutated versions with improved binding affinity to HLA molecules. Specifically, anchor residues in the peptide sequence are altered to enhance stability and immunogenicity, transforming the peptide's interaction parameters with the immune system to overcome the limitation of conventional treatments that fail to induce specific immune responses
Solution Approach 2:
The patent creates composite immunogenic compositions by combining multiple mutated WT1 peptides with different HLA binding specificities into single vaccine formulations. These composite compositions contain peptides designed to bind to various HLA class I and class II molecules, enabling broad immune coverage and simultaneously addressing the need for specific immune response induction across different patient populations
2Reliability
If mutated WT1 peptides with specific binding motifs are designed, then immune response induction is improved, but peptide design complexity increases
Solution Approach 1:
The patent applies segmentation by dividing the WT1 protein sequence into multiple discrete peptide segments, each optimized for specific HLA molecule binding. Rather than attempting to design a single complex peptide, the approach segments the antigen into manageable units (e.g., 9-mer, 10-mer, 11-mer peptides) with specific anchor residues tailored for different HLA alleles, simplifying the design process while maintaining high immunogenicity
Solution Approach 2:
The patent achieves universality by designing mutated WT1 peptides with conserved binding motifs that can bind to multiple HLA class I and class II molecules. The peptides are engineered with anchor residues that accommodate variations in HLA binding grooves, allowing a single peptide design to function across different HLA types and reducing the overall complexity of creating patient-specific formulations
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
The peptides and compositions effectively stimulate immune responses, leading to the proliferation of WT1 protein-specific T cells, which can recognize and target WT1-expressing cancer cells, potentially reducing cancer incidence and progression.
Implementation Method 1
comprising: (a) a binding motif of a human leukocyte antigen (HLA) Class II molecule; and (b) a binding motif of an HLA class I molecule
Implementation Method 2
designed to induce immune responses by stimulating CD8+ and CD4+ lymphocytes, thereby targeting WT1-expressing cancers
Data Source
AI summary
This invention provides peptides, immunogenic compositions and vaccines comprising same, and methods of treating, reducing the incidence of, and inducing immune responses to a WT1-expressing cancer, comprising same.