GPC3-Derived Peptides for Broad HLA Binding
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Solution Overview
Problem
Current peptides with HLA-binding capacity are limited in their ability to treat or prevent cancer, particularly due to the high polymorphism of the HLA gene, which requires peptides adaptable to multiple HLA types.
Innovation Solution
Development of immunogenic peptides derived from GPC3, specifically designed to bind to HLA class I molecules, inducing CTL responses, and used in pharmaceutical compositions and immunity inducers to treat or prevent cancer, with modifications to enhance binding to multiple HLA types.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional peptides with HLA-binding capacity are used, then some immunogenicity is achieved, but the ability to treat or prevent cancer is limited due to HLA gene polymorphism
Solution Approach 1:
The patent develops peptides that can bind to multiple HLA class I molecule types (including HLA-A*02:01, HLA-A*24:02, and other alleles) simultaneously. This multi-functional capability allows a single peptide formulation to serve multiple patient populations with different HLA genotypes, thereby resolving the contradiction between treatment efficacy and HLA type compatibility.
Solution Approach 2:
The patent employs structure-activity relationship analysis to systematically modify peptide amino acid sequences, optimizing binding affinity across multiple HLA alleles. By changing specific amino acid parameters at key positions (such as positions 2, 9, and 11), the peptides achieve broad HLA binding capacity while maintaining immunogenicity, thus resolving the contradiction between reliability and adaptability.
2Adaptability or versatility
If peptides are designed to bind to multiple HLA types, then patient coverage is improved, but peptide design complexity increases
Solution Approach 1:
The patent divides the peptide design process into systematic segments: (1) identification of conserved HLA-binding motifs, (2) selection of candidate amino acid sequences from GPC3, (3) in silico binding prediction to multiple HLA alleles, and (4) experimental validation. This segmented approach reduces design complexity by breaking down the complex multi-HLA optimization problem into manageable steps.
Solution Approach 2:
The patent performs preliminary computational screening and binding affinity prediction for multiple HLA alleles before synthesizing and testing peptides experimentally. This preliminary action filters out non-viable candidates in silico, reducing the number of experimental iterations needed and thereby reducing overall design complexity while maintaining broad patient coverage.
Data Source
AI summary
The present invention provides a peptide containing 8 or more consecutive amino acid residues in an amino acid sequence of any of SEQ ID NOS: 1 to 11 and consisting of 11 or less amino acid residues.