Native and Optimized Peptide Vaccination for Antitumor Immunity
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Solution Overview
Problem
Current cancer vaccines primarily target dominant peptides, which have low efficacy due to tolerance issues, while cryptic peptides, with optimized immunogenicity, can induce antitumor immunity but require innovative approaches to maintain and boost the immune response effectively.
Innovation Solution
A vaccination protocol involving a native peptide following optimized peptide vaccination to select and boost CTLs with high specificity for tumor cells, using a combination of optimized and native cryptic peptides to enhance antitumor immunity without inducing autoimmunity against normal tissues.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If optimized cryptic peptides are used to induce antitumor immunity, then immunogenicity is improved, but maintaining and boosting the immune response becomes difficult
Solution Approach 1:
The patent applies preliminary action by first vaccinating with optimized cryptic peptides to initiate the immune response, then subsequently administering native peptides to maintain and boost the response. This two-stage approach ensures the immune system is first activated by the highly immunogenic optimized peptide, then sustained by the native peptide that mimics the natural tumor antigen structure.
Solution Approach 2:
The patent changes the peptide parameters between vaccination stages - using optimized peptides with modified amino acid sequences for initial vaccination to maximize immunogenicity, then switching to native peptides with natural sequences for maintenance. This parameter change allows exploitation of both the enhanced immunogenicity of optimized peptides and the natural recognition of native peptides by the immune system.
2Duration of action of moving object
If native peptides are used for vaccination, then immune response maintenance is improved, but immunogenicity is reduced due to tolerance
Solution Approach 1:
The patent reverses the conventional approach by performing preliminary vaccination with optimized cryptic peptides that have high immunogenicity and can break tolerance, before subsequently using native peptides for maintenance. This preliminary exposure to optimized peptides primes the immune system to recognize and respond to native peptides without tolerance interference.
Solution Approach 2:
The optimized cryptic peptide acts as an intermediary that bridges the gap between the immune system's tolerance to native peptides and the need for sustained immune response. The optimized peptide with modified sequences serves as a mediator that can initiate strong immune responses, which are then directed against native tumor antigens.
3Reliability
If optimized peptides are used to stimulate CTLs, then antitumor immunity is improved, but autoimmunity against normal tissues may be induced
Solution Approach 1:
The patent applies local quality by making localized modifications to specific amino acid positions in the peptide sequence (particularly at anchor residues that bind to HLA molecules) to enhance immunogenicity, while leaving the rest of the peptide sequence intact or minimally modified. This allows enhancement of immune recognition at specific critical positions without altering the overall antigen specificity that could trigger autoimmunity.
Solution Approach 2:
The patent carefully changes specific parameters of the peptide sequence (amino acid substitutions at key positions) to optimize HLA binding and immunogenicity, while maintaining the overall structural and sequence features that define tumor-specific antigen recognition. This selective parameter change enhances antitumor immunity while preserving tolerance to normal tissues.
Data Source
AI summary
The present invention pertains to the field of vaccination, and more particularly to the fields of antitumor and antiviral vaccination. The invention relates to the use of a native peptide in a medicinal composition, for selecting and/or boosting part of a CTL immune response which has been initiated by an optimized immunogenic peptide derived from said native peptide. The invention also concerns vaccination kits which comprise several doses of optimized peptides and of their cognate native peptides.