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Publication Number
US-12311018-B2
Publication Date
2025-05-27
Expiration Date
Abstract
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.
Core Innovation
The invention relates to a method of stimulating an immune response in a patient by generating a recombinant nucleic acid encoding a polytope. The polytope includes a plurality of filtered neoepitope sequences that are filtered in silico by comparing tumor versus matched normal control of the same patient, and the neoepitope sequences are further filtered in silico to have binding affinity to MHC-II of equal or less than 200 nM.
The recombinant nucleic acid further comprises a trafficking element that directs the polytope to a sub-cellular location selected from recycling endosome, sorting endosome, and lysosome. The polytope is encoded in a single recombinant nucleic acid and is configured to enable intracellular routing toward the selected compartment for immune stimulation.
The method includes cloning the recombinant nucleic acid into an adenoviral vector, formulating the recombinant adenovirus into an immune therapy composition, and administering the immune therapy composition to the patient by intravenous injection. The document also describes immune therapy compositions that can incorporate additional immune-modulatory coding sequences, including co-stimulatory molecules, stimulatory cytokines, and checkpoint-inhibition interfering proteins.
Claims Coverage
The partial content provides one independent claim. The inventive features cover patient-matched in silico neoepitope filtering for MHC-II, polytope-directed intracellular trafficking to specified sub-cellular compartments, adenoviral-vector cloning and immune-therapy formulation, and intravenous administration.
In silico tumor versus matched normal neoepitope polytope selection for MHC-II affinity
Generating a recombinant nucleic acid encoding a polytope comprising a plurality of filtered neoepitope sequences filtered in silico by comparing tumor versus matched normal control of the same patient, and filtered in silico to have binding affinity to MHC-II of equal or less than 200 nM.
Trafficking element directing the polytope to recycling endosome, sorting endosome, or lysosome
Including a trafficking element in the recombinant nucleic acid that directs the polytope to a sub-cellular location selected from the group consisting of a recycling endosome, a sorting endosome, and a lysosome.
Adenoviral-vector cloning of the trafficking polytope nucleic acid
Cloning the recombinant nucleic acid into an adenoviral vector.
Immune therapy formulation and intravenous administration of recombinant adenovirus
Formulating the recombinant adenovirus into an immune therapy composition and administering the immune therapy composition to the patient by intravenous injection.
The core coverage combines patient-matched in silico filtering of neoepitopes for MHC-II binding affinity with a trafficking element that routes the polytope to recycling endosomes, sorting endosomes, or lysosomes, and delivery as a recombinant adenoviral immune therapy administered intravenously.
Stated Advantages
Not explicitly described in patent.
Documented Applications
Not explicitly described in patent.
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