RNA-Edited Neoantigen Epitopes for Shared Tumor Immunotherapy
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Solution Overview
Problem
Current neoantigen-based immunotherapies face challenges due to personalized characteristics, high production costs, low accuracy in prediction, and immunogenicity regulation by immunoediting, limiting their widespread application and effectiveness.
Innovation Solution
A preparation method involving RNA editing technology to introduce site-directed mutations into tumor antigens, generating neoantigenic epitopes that are shared and specific to tumors but not normal tissues, using systems like MS2-MCP2, LEAPER, and λN-BoxB to enhance immunotherapy responsiveness.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If personalized neoantigen vaccines are developed for each patient, then tumor specificity and immunogenicity are improved, but production costs and complexity increase significantly
Solution Approach 1:
The patent applies universality by developing a standardized neoantigen vaccine platform that can target multiple tumor types and personalized neoantigens through a common delivery system. The vaccine composition includes standardized components (emulsifier, adjuvant, immunostimulating nucleic acid) that can be combined with different neoantigen peptides to create personalized vaccines without requiring separate development for each patient, thus reducing production complexity while maintaining tumor specificity
2Loss of information
If current neoantigen prediction technology is used, then epitopes can be identified, but prediction accuracy remains low
Solution Approach 1:
The patent applies feedback by incorporating immunostimulating nucleic acids that enhance the immune response to neoantigens, creating a system where the immune system itself provides feedback on epitope effectiveness. The composition includes nucleic acids that stimulate dendritic cells and T cells, allowing for better identification of functional epitopes through immune response measurement rather than relying solely on computational prediction accuracy
3Reliability
If tumor antigens are targeted under immunoediting pressure, then immunotherapy efficacy is enhanced, but tumor escape mechanisms reduce effectiveness
Solution Approach 1:
The patent applies preliminary anti-action by incorporating multiple immunostimulating nucleic acids and adjuvants that proactively enhance the immune response before tumors can escape. The composition includes cyclic GMP-AMP synthase (cGAS) stimulators and other immunomodulators that create a strong preemptive immune environment, making it harder for tumors to downregulate or escape from immune surveillance through immunoediting mechanisms
Data Source
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AI summary
Disclosed is a preparation method for an antigenic epitope. The preparation method comprises the following step: using RNA editing to perform site-directed mutagenesis on a tumor antigen to obtain a neoantigen epitope. The generated neoantigen has the sharing property, avoiding the inaccuracy of identifying a tumor personalized neoantigen, and reducing development costs. An RNA editing system that is safer and more controllable than the DNA editing is used, the editing targets mRNA rather than genomic DNA, and an editing result is reversible and controllable.