Polytope Vaccine Design for Enhanced Antigen Presentation
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Solution Overview
Problem
Current cancer immunotherapies targeting common cancer antigens often fail to elicit a therapeutic response due to insufficient quantities of immune effector cells, exhaustion of these cells, and variability in antigen processing and presentation across patients. Additionally, the large number of unique cancer neoepitopes makes it challenging to identify effective therapeutic targets.
Innovation Solution
The development of immune therapeutic compositions and methods that combine multiple neoepitopes into a rational-designed polypeptide with a trafficking signal to enhance antigen processing and presentation. This approach utilizes multiple vaccine modalities, including DNA, bacterial, and yeast vaccines, to provide distinct immune stimulatory effects and significantly shorten the time-to-first-vaccination.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If multiple neoepitopes are expressed individually in antigen presenting cells, then each neoepitope can be processed and presented separately, but the overall therapeutic efficacy is reduced due to insufficient immune stimulation and lack of synergistic effects
Solution Approach 1:
The patent merges multiple neoepitopes into a single polytope polypeptide structure. This polytope contains multiple neoepitope sequences that are processed and presented together by antigen presenting cells, creating synergistic immune stimulation. The combined structure allows simultaneous presentation of multiple tumor-specific antigens, enhancing the overall therapeutic efficacy compared to individual neoepitope expression.
Solution Approach 2:
The invention creates a composite polypeptide structure (polytope) that integrates multiple neoepitope sequences into a single functional unit. This composite structure combines the immunogenic properties of different neoepitopes, allowing the immune system to recognize multiple tumor-specific targets simultaneously, thereby improving reliability of therapeutic response.
2Reliability
If viral vectors are used to express neoepitopes, then high specificity towards patient and tumor is achieved, but production time is excessively long (6-8 weeks or more) which is prohibitive for fast-growing cancers
Solution Approach 1:
The patent extracts the essential function of viral vectors (neoepitope expression) and implements it through non-viral systems. By using plasmid DNA or synthetic polypeptide constructs instead of viral vectors, the invention eliminates the lengthy viral production process while maintaining the ability to express neoepitopes specifically in patient cells. This reduces production time from 6-8 weeks to a much shorter timeframe.
Solution Approach 2:
The invention employs disposable plasmid DNA or synthetic polypeptide constructs that can be rapidly produced and administered without the need for complex viral vector production infrastructure. These non-viral carriers are simpler, faster to manufacture, and can be produced on-demand, addressing the time constraint for treating fast-growing cancers while maintaining therapeutic specificity.
3Adaptability or versatility
If the number of neoepitope targets is increased to cover more cancer variants, then the coverage of tumor-specific antigens is improved, but the complexity of identifying and validating effective targets increases
Solution Approach 1:
The patent creates a universal polytope platform that can accommodate multiple neoepitope sequences targeting different cancer variants. This multi-functional structure allows a single therapeutic formulation to address multiple tumor-specific antigens simultaneously, improving coverage across cancer variants without requiring separate identification and validation processes for each target.
Solution Approach 2:
The invention segments the polytope polypeptide into multiple distinct neoepitope sequences, each targeting specific cancer variants. This segmentation allows the system to cover a broad range of cancer types and mutations while maintaining a standardized delivery platform. The modular structure simplifies the process of adding new neoepitopes to the polytope without increasing overall system complexity.
4Productivity
If immune effector cell quantities are increased to overcome exhaustion, then the immune response strength is improved, but the risk of immune-related adverse events increases
Solution Approach 1:
The patent applies local quality by directing immune stimulation specifically to tumor tissues through neoepitope-specific T-cell recognition. The polytope expresses tumor-specific antigens that are uniquely processed and presented by tumor cells, allowing immune effector cells to be activated locally at the tumor site rather than systemically. This localized immune response increases efficacy while reducing off-target toxicity and immune-related adverse events.
Data Source
AI summary
Systems and methods are presented that allow for selection of tumor neoepitopes that are then used to generate recombinant nucleic acids that encode one or more polytopes that are optimized for proper trafficking and processing. In preferred methods, the polytopes are encoded in a plasmid and/or a viral expression system for use as a therapeutic agent.