Multiepitope Polypeptide Vaccine for Trispecific CTL Response
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current anti-cancer vaccines based on dominant tumor peptides elicit weak immunological and clinical responses due to tolerance issues and genetic instability of tumors, and fail to induce polyspecific cytotoxic T lymphocyte responses, limiting their effectiveness.
Innovation Solution
A polypeptide comprising optimized cryptic tumor peptides TERT988Y, HER-2/neu402Y, and MAGE-A248V9, specifically arranged with spacers to enhance immunogenicity, is used to induce a polyspecific CTL response, with the polypeptide being optimized for processing and presentation to the immune system.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of manufacture
If dominant tumor peptides are used in anti-cancer vaccines, then the vaccine structure is simple and easy to manufacture, but the immunological response is weak due to tolerance issues
Solution Approach 1:
The patent modifies the peptide sequences by introducing optimized cryptic peptides with altered amino acid compositions that escape central tolerance mechanisms. Specifically, peptides like TERT988Y, HER-2/neu402Y, and MAGE-A248V9 are designed with specific anchor residues and flanking sequences that enhance MHC class I binding affinity while avoiding thymic deletion, thereby transforming the immunogenic parameters without changing the overall vaccine platform
Solution Approach 2:
The vaccine combines multiple optimized cryptic peptides derived from different tumor antigens (TERT, HER-2/neu, MAGE-A) into a single polypeptide construct. This composite approach ensures polyspecific CTL responses against multiple tumor-associated antigens simultaneously, overcoming the limitation of single-peptide vaccines while maintaining manufacturing feasibility through recombinant expression systems
2Device complexity
If single epitope vaccines are used, then the vaccine design is simple, but the response is restricted to one antigen which may not be expressed by all tumor cells
Solution Approach 1:
The patent designs a multiepitope polypeptide vaccine that simultaneously presents multiple optimized cryptic peptides from different tumor antigens (TERT, HER-2/neu, MAGE-A). This single vaccine construct performs multiple functions: it elicits CTL responses against diverse tumor types expressing any of these antigens, provides broad-spectrum coverage, and maintains a unified delivery platform, thereby achieving universality without proportionally increasing complexity
3Reliability
If optimized cryptic peptides are combined in polypeptides, then the immunogenicity is enhanced and polysspecific CTL response is induced, but the polypeptide structure and processing requirements become more complex
Solution Approach 1:
The patent divides the multiepitope construct into distinct segments corresponding to individual optimized cryptic peptides (TERT988Y, HER-2/neu402Y, MAGE-A248V9), each separated by cleavage sites recognized by proteases such as proteasome or caspases. This segmentation allows cellular processing machinery to independently process each epitope segment for MHC class I presentation, ensuring reliable immunogenicity while managing structural complexity through modular design with standardized linkers and processing signals
Data Source
AI summary
The present invention pertains to the field of anti-cancer vaccines. More particularly, the invention concerns an optimized polypeptide, which comprises three cryptic tumor peptides with enhanced immunogenicity and comprises the amino acids sequence YLQVNSLQTVYLEYRQVPVYLEEITGYL (SEQ ID NO. 2), for use in an anti-cancer vaccine. Nucleic acids encoding such a polypeptide, as well as complexes and dendritic cells engineered with this polypeptide or a nucleic acid encoding it, are also part of the invention.