Neoantigen Engineering via Splice Modulating Oligonucleotides
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Solution Overview
Problem
Current cancer vaccine and immunotherapy treatments require characterization of a patient's tumor gene expression and epitope profile, making them costly and time-consuming, limiting their application to specific cancer types and patient groups.
Innovation Solution
Engineering peptide epitopes in cancer cells using RNA modifying oligonucleotides, such as splice modulating or RNA editing oligonucleotides, to generate aberrant RNA transcripts that encode aberrant polypeptides, which are then displayed on the cell surface or secreted, triggering an immune response independent of the endogenous epitope profile.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If patient-specific cancer vaccines are developed based on tumor gene expression and epitope profile characterization, then the therapeutic specificity and effectiveness are improved, but the development time and cost increase significantly
Solution Approach 1:
The patent applies preliminary action by pre-defining a panel of candidate epitopes and their corresponding mRNA sequences before treatment. The composition includes multiple epitopes with different MHC class II restrictions, allowing rapid deployment without time-consuming personalized characterization of each patient's tumor epitope profile.
Solution Approach 2:
The patent changes the approach from patient-specific epitope identification to a standardized panel of pre-selected epitopes. This parameter change allows the therapy to be applied across different patient groups without requiring individualized epitope characterization, thereby reducing development time while maintaining therapeutic relevance.
2Reliability
If patient-specific cancer vaccines are developed based on tumor gene expression and epitope profile characterization, then the therapeutic specificity are improved, but the cost increases significantly
Solution Approach 1:
The patent applies universality by creating a multi-functional composition that can treat multiple cancer types and patient groups simultaneously. The panel of epitopes is designed to cover various MHC class II restrictions and tumor-associated antigens, making the therapy applicable across different indications without requiring separate development for each patient-specific scenario.
Solution Approach 2:
The patent changes the development paradigm from costly patient-specific epitope characterization to a standardized panel approach. This parameter change enables manufacturing and deployment at lower cost while maintaining therapeutic specificity through the curated selection of immunogenic epitopes known to elicit robust T-cell responses.
3Reliability
If current immunotherapy treatments are used, then the immune response is stimulated, but the application is limited to specific cancer types and patient groups
Solution Approach 1:
The patent applies universality by designing a composition that can be applied across multiple cancer types and patient groups. The panel of epitopes includes tumor-associated antigens from various cancer types, and the formulation can be administered to patients with different MHC class II restrictions, thereby expanding adaptability while maintaining immune response generation.
Solution Approach 2:
The patent changes the scope of application from limited to broad by pre-selecting a diverse panel of epitopes that represent multiple cancer types and MHC restrictions. This parameter change enables the therapy to adapt to different patient populations without requiring re formulation, thereby increasing versatility while preserving immunogenicity.
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
This approach enables a broader application of cancer therapies by selectively targeting cancer cells with engineered neo-antigens, potentially leading to a durable and strong anti-tumor immune response without the need for patient-specific therapies.
Implementation Method 1
RNA modifying oligonucleotides include splice modifying oligonucleotides which alter the splicing of the target pre-mRNA
Implementation Method 2
or RNA editing oligonucleotides, which can introduce insertions, deletions of substitutions (such as A to G substitutions)
Implementation Method 3
The ABO blood group antigens are among the most important carbohydrate antigens in the immune system. The A and B blood group antigens are formed by the addition of specific sugar moieties to a common core structure on the surface of red blood cells
Implementation Method 4
Tumor-associated carbohydrate antigens (TCA) are a group of cell surface molecules that are differentially expressed on tumor cells compared to normal cells
Data Source
AI summary
The invention relates to the field of immunotherapy and vaccine treatment of diseased cells via enhancing the immune response to the diseased cells. In the context of the present invention this is done by engineering neo-antigens in cells via oligonucleotide mediated production of aberrant RNA transcripts which, when transcribed in the cell, result in the generation or increased expression of aberrant polypeptides. Extracellular display of these polypeptides, of peptide fragments derived provides antigen epitopes (neoantigen) for detection by the immune system.