HER3 Immunogenic Peptides for CD4+ T Cell Activation
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Solution Overview
Problem
Current immunotherapeutic approaches are inadequate for effectively generating immune responses against HER3, a key protein associated with breast cancer and other malignancies, limiting the treatment options for cancers with HER3 overexpression.
Innovation Solution
Development of isolated peptides from the HER family proteins, including HER3, which are immunogenic and capable of activating CD4 T cells, used in vaccines to stimulate an immune response and induce anti-tumor immunity.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If current immunotherapeutic approaches are used to target HER3, then treatment options are limited, but the ability to generate effective immune responses is inadequate
Solution Approach 1:
The patent segments the HER3 protein into multiple overlapping peptides (15-mer peptides with 10 amino acid overlaps) to create a comprehensive peptide library. This segmentation allows for identification of specific immunogenic epitopes that can be targeted by the immune system, thereby improving the reliability of immune responses while providing versatile treatment options through multiple potential targets.
Solution Approach 2:
The patent employs parameter changes by systematically varying peptide sequences and testing them against diverse HLA-DR supertypes (1-7). This approach identifies peptides with broad binding affinity across different MHC class II molecules, enhancing both the effectiveness and versatility of immunotherapeutic strategies by accommodating genetic diversity in the patient population.
2Reliability
If isolated immunogenic peptides from HER family proteins are developed, then robust immune responses including IFN-γ production and CD4+ Th1 cell activation are elicited, but the complexity of peptide identification and validation increases
Solution Approach 1:
The patent performs preliminary action by pre-screening peptides for binding affinity to multiple HLA-DR supertypes before in vivo testing. This pre-selection process identifies high-probability immunogenic candidates, reducing the complexity of subsequent validation steps while ensuring robust immune responses are elicited by pre-validated peptides.
Solution Approach 2:
The patent develops a universal peptide screening platform that tests against seven different HLA-DR supertypes simultaneously. This multi-functional approach identifies peptides with broad applicability across diverse genetic backgrounds, simplifying the overall identification process by finding universally effective candidates rather than requiring separate validation for each HLA type.
3Adaptability or versatility
If peptides are designed to bind to multiple HLA-DR supertypes, then broad immune response coverage is achieved, but the precision of targeting specific epitopes decreases
Solution Approach 1:
The patent applies local quality by identifying specific anchor residues within peptides that are critical for binding to particular HLA-DR supertypes. This allows for precise optimization of peptide sequences to target specific epitopes with high accuracy while maintaining the ability to bind multiple supertypes, thus preserving both precision and versatility.
Solution Approach 2:
The patent employs a dynamic approach by creating a hierarchical selection process that first identifies peptides with broad supertype coverage, then refines selection based on specific epitope targeting precision. This multi-stage dynamic filtering optimizes both HLA supertype coverage and epitope targeting accuracy, balancing the two competing requirements.
Data Source
AI summary
The invention provides compositions, methods, and vaccines that may stimulate the immune system and that may be used for treating malignancies associated with overexpression of the HER3 protein. Such compositions include epitopes of the HER3 protein.