Melanoma Antigen Peptides for Robust CD4 T Cell Response
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Solution Overview
Problem
Current peptide-based cancer vaccines, particularly in melanoma, face challenges due to suboptimal design and immune suppressive mechanisms, leading to vanishing CTL responses and tolerance towards targeted antigens, with a need for more effective induction of robust CD8 and CD4 anti-tumor T cell responses.
Innovation Solution
Identification of new epitopes along the MELOE-1 sequence with a T helper profile for CD4 T cell response, specifically amino acid sequences that can bind to HLA molecules and induce cellular or humoral responses, used in the prevention or treatment of melanoma.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of manufacture
If short epitopic peptides are used in peptide-based cancer vaccines, then the vaccine design is simple and manufacturing is easier, but the CTL responses vanish and tolerance is induced towards targeted antigens
Solution Approach 1:
The patent segments the MELOE-1 antigen into multiple overlapping peptides of different lengths (15-20 amino acids) that collectively cover the entire antigen sequence. This segmentation allows the vaccine to present multiple epitopes to the immune system, ensuring both CD8+ CTL and CD4+ T cell responses while maintaining manageable vaccine design and manufacturing complexity
Solution Approach 2:
The patent transitions from using single short peptides to a multi-dimensional approach by incorporating peptides of varying lengths (15, 16, 17, 18, 19, 20 amino acids) that overlap to cover the complete MELOE-1 sequence. This dimensional expansion in peptide length diversity enables simultaneous engagement of different T cell subsets while maintaining manufacturing feasibility
2Reliability
If class I HLA-restricted peptides are used to stimulate CD8 CTL responses, then the anti-tumor immune response mechanism is targeted, but the clinical impact remains modest due to immune suppressive mechanisms
Solution Approach 1:
The patent merges class I HLA-restricted peptides (for CD8+ CTL response) with class II HLA-restricted peptides (for CD4+ T cell response) into a single unified vaccine composition. This combination leverages the cytotoxic activity of CD8+ T cells while simultaneously engaging CD4+ T cells that provide help for enhanced CTL responses and direct antitumor effects, thereby overcoming immune suppression and improving clinical efficacy
Solution Approach 2:
The vaccine composition functions as a composite immunological material by integrating multiple peptide types with different HLA restrictions. This composite approach creates a synergistic effect where class I and class II restricted peptides work together to generate both direct cytotoxicity and helper functions, addressing the limitation of modest clinical impact from single-component vaccines
3Reliability
If CD4+ T cells are engaged to provide help for CD8+ CTL priming, then robust anti-tumor immunity is enhanced, but the vaccine design complexity increases
Solution Approach 1:
The patent employs overlapping peptides of standardized lengths (15-20 amino acids) that serve multiple functions simultaneously: they can be presented by both class I and class II HLA molecules, stimulate both CD8+ and CD4+ T cells, and provide both direct cytotoxicity and helper functions. This multi-functionality reduces design complexity compared to creating separate peptide sets for different T cell subsets
Data Source
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AI summary
The present invention relates to a melanoma antigen peptide comprising the amino acids sequence selected in the group consisting of SEQ ID NO: 10, SEQ ID NO: l l, SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 14 or SEQ ID NO: 15 or a function-conservative variant thereof. Moreover the invention also relates to a melanoma antigen peptide according to the invention for use in the prevention or the treatment of melanoma in patient.