HSP70-Derived Peptides for Broad HLA Binding and CTL Induction

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Solution Overview

Problem

Existing peptides with HLA-binding capacity are limited in their applicability across different HLA types, necessitating the development of peptides that can induce cytotoxic T cells (CTLs) for broad cancer treatment and prevention, particularly considering the polymorphism of HLA genes.

Innovation Solution

Development of immunogenic peptides derived from HSP70, specifically designed to bind to multiple HLA types, including HLA-A*24:02, HLA-A*02:01, and HLA-A*02:06, with sequences ranging from 8 to 11 amino acids, capable of inducing CTLs and used in pharmaceutical compositions, immunity inducers, and methods for producing antigen-presenting cells.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If peptides are designed to bind to specific HLA types, then HLA-binding capacity is improved, but adaptability to multiple HLA types deteriorates

Engineering Contradiction:

ImproveHLA-binding capacityVSAvoidadaptability to multiple HLA types

Core Design Contradiction:

ReliabilityVSAdaptability or versatility

Solution Approach 1:

The patent designs peptides with amino acid sequences that can bind to multiple HLA class I molecules (HLA-A*02:01, HLA-A*24:02, HLA-A*02:06) simultaneously. The peptide sequences are selected from HSP70-derived regions and optimized to have broad HLA binding promiscuity, allowing a single peptide to serve multiple HLA types rather than requiring separate peptides for each HLA allele.

Inventive Principle:

Principle #6Universality (Multi-functionality)

Solution Approach 2:

The patent modifies peptide parameters including amino acid sequence selection from HSP70 regions, length (8-11 residues), and specific residue compositions to optimize binding affinity across multiple HLA types. By changing the amino acid sequence parameters and selecting specific HSP70-derived regions, the peptides achieve both high binding capacity and broad adaptability.

Inventive Principle:

Principle #35Parameter changes

2Reliability

If peptides are derived from HSP70 with specific sequences, then CTL-inducing capability is improved, but manufacturing complexity increases

Engineering Contradiction:

ImproveCTL-inducing capabilityVSAvoidmanufacturing complexity

Core Design Contradiction:

ReliabilityVSDevice complexity

Solution Approach 1:

The patent extracts specific immunogenic peptide sequences from the HSP70 protein sequence. Rather than using the entire HSP70 protein or complex formulations, the invention isolates and uses only the critical 8-11 amino acid residues that are responsible for HLA binding and CTL induction, simplifying manufacturing while maintaining immunogenicity.

Inventive Principle:

Principle #2Taking out (Extraction)

Solution Approach 2:

The HSP70 protein sequence is segmented into multiple potential peptide regions, from which specific 8-11 residue sequences are selected based on their HLA binding potential and immunogenicity. This segmentation allows the patent to identify and produce only the most effective peptide sequences rather than dealing with the entire protein.

Inventive Principle:

Principle #1Segmentation

Data Source

PatentUS12448413B2HSP70-derived peptide, pharmaceutical composition for treating or preventing cancer using same, immunity inducer, and method for producing antigen presenting cell

Publication Date: 2025.10.21 NEC CORP

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 15 and consisting of 11 or less amino acid residues.