HLA-A*1101-Restricted WT1 Peptide for Cancer Immunotherapy
Solution Overview
Problem
There is a need for an HLA-A*1101-restricted WT1 peptide that can bind to the HLA-A*1101 molecule and induce WT1-specific cytotoxic T lymphocytes (CTLs) for the treatment and prevention of cancer, as existing peptides are limited to specific MHC class I subtypes.
Innovation Solution
A peptide comprising an amino acid sequence of 9 contiguous amino acids from the WT1 protein, specifically designed to bind to the HLA-A*1101 molecule, and a peptide dimer formed by disulfide bonding of WT1 protein monomers, which can induce WT1-specific CTLs in subjects positive for HLA-A*1101.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Adaptability or versatility
If existing WT1 peptides are used for cancer treatment, then CTL induction is achieved, but the peptides are limited to specific MHC class I subtypes (HLA-A*0201, HLA-A*2402, HLA-A*2601, HLA-A*3303)
Solution Approach 1:
The patent identifies and characterizes a new HLA-A*1101-restricted WT1 peptide (amino acids 251-259: AAGSSSSVK) with distinct binding parameters and affinity characteristics compared to previously known peptides. This expands the repertoire of MHC-restricted peptides by discovering a new binding specificities parameter set for HLA-A*1101, enabling vaccine formulation for this previously uncovered MHC subtype.
2Reliability
If a peptide is designed to bind to HLA-A*1101, then CTL induction capability is improved, but the peptide must be specifically tailored to this MHC subtype
Solution Approach 1:
The patent segments the WT1 protein into multiple potential peptide regions and systematically evaluates their binding affinity to HLA-A*1101. By dividing the protein sequence into overlapping peptides (e.g., amino acids 251-259, 260-268, etc.) and assessing each segment's binding properties, the invention identifies the optimal peptide segment (251-259) that achieves reliable CTL induction with the highest binding affinity.
3Productivity
If WT1 peptide vaccination is administered, then cancer treatment efficacy is enhanced, but the peptide must be synthesized with high precision to ensure proper binding
Solution Approach 1:
The patent employs computer-based prediction algorithms and modeling to simulate and copy the binding interface between the WT1 peptide (AAGSSSSVK) and HLA-A*1101 molecule. By creating digital models of the peptide-MHC complex and evaluating binding affinity through computational methods, the invention optimizes the peptide sequence and structure before synthesis, ensuring high manufacturing precision and reliable binding without requiring extensive trial-and-error synthesis.
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 effectively induce WT1-specific CTLs in a wide range of subjects, particularly those with the HLA-A*1101 allele, demonstrating high cytotoxic activity against cancer cells expressing the WT1 gene while sparing normal cells, thus providing a broad-spectrum cancer treatment option.
Implementation Method 1
the peptide has an ability to bind to an HLA-A*1101 molecule
Implementation Method 2
two peptide monomers each comprising an amino acid sequence consisting of 9 contiguous amino acids from a WT1 protein and comprising at least one cysteine residue are bound to each other through a disulfide bond
Implementation Method 3
the induced CTLs have a cytotoxic activity specific for tumor cells expressing endogenously a WT1 gene at high levels
Data Source
AI summary
An HLA-A*1101-restricted WT1 peptide, specifically, a peptide comprising an amino acid sequence consisting of 9 contiguous amino acids from a WT1 protein, wherein the peptide has an ability to bind to an HLA-A*1101 molecule, and has an ability to induce a CTL is described. A peptide dimer having an ability to bind to an HLA-A*1101 molecule and having an ability to induce a CTL, in which two peptide monomers each comprising an amino acid sequence consisting of 9 contiguous amino acids from a WT1 protein and comprising at least one cysteine residue are bound to each other through a disulfide bond is also described. Furthermore, a polynucleotide encoding the peptide, a pharmaceutical composition for the treatment and/or prevention of a cancer comprising the same and the like are provided.