Tumor-specific neoantigens and methods of using the same
Inventors
Duperret, Elizabeth Kennedy • PUCHALT, ALFREDO PERALES • Weiner, David • Sardesai, Niranjan Y.
Assignees
Geneos Therapeutica Inc • The Wistar Institute • Inovio Pharmaceuticals Inc • Geneos Therapeutics Inc
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Publication Number
US-12528848-B2
Publication Date
2026-01-20
Expiration Date
Abstract
The disclosure relates to methods of manufacturing individualized vaccines that comprise nucleic acid molecules that encode one or more neoantigens specific for antigens that are expressed by a tumor in a subject. Compositions comprising coding regions encoding neoantigens organized in a pattern of nucleic acid sequences are also disclosed as well as methods of immunizing a subject using the same.
Core Innovation
The disclosure describes nucleic acid molecules encoding a chimeric polypeptide comprising a concatemer of linked cancer neoantigens or antigenic determinants. The construct comprises independently selected antigen expression domains separated by linkers encoding furin cleavage sites, operably linked to a regulatory sequence in a DNA backbone comprising SEQ ID NO:68 or a multiple cloning site. Neoantigens are selected from tumor-versus-normal sequencing and ranked using HLA, T-cell receptor, or TAP binding characteristics.
Methods administer the nucleic acid molecules to treat cancer or enhance an immune response against heterogeneous hyperproliferative cells expressing the encoded neoantigens. Reported evaluations describe predominantly CD8+ T-cell responses, selective killing of mutated tumor cells, and delayed tumor progression across tumor models including TC1, B16, CT26, LLC, and ID8. The background problem being solved is not explicitly described in patent.
Claims Coverage
The two independent claims are claims 1 and 16, covering two inventive features directed to cancer treatment and immune-response enhancement.
Cancer treatment using a neoantigen-encoding nucleic acid
Independent claim 1 covers administering to a subject having cancer a nucleic acid molecule encoding a chimeric polypeptide comprising a concatemer of linked cancer neoantigens or antigenic determinants, with independently selected antigen expression domains separated by linkers encoding furin cleavage sites within a DNA backbone region comprising a regulatory sequence and a multiple cloning site or SEQ ID NO:68.
Enhancing an immune response against heterogeneous hyperproliferative cells
Independent claim 16 covers administering a nucleic acid molecule encoding a chimeric polypeptide comprising a linked series of neoantigens or antigenic determinants to enhance an immune response against heterogeneous hyperproliferative cells expressing those antigens, relative to a control nucleic acid molecule free of a neoantigen-encoding sequence.
The independent claims cover cancer treatment and enhancement of an immune response using nucleic acid molecules that encode linked neoantigens or antigenic determinants joined by furin-cleavage-site linkers within a defined DNA backbone.
Stated Advantages
Therapeutic outcomes including tumor regression or shrinkage, inhibiting or retarding tumor growth, tumor necrosis or cell death, prevention or delay of tumor recurrence or spread, and tumor elimination.
Increased or prolonged anti-tumor T-cell activity, including increased numbers of anti-tumor or activated T cells compared with before treatment.
Enhancement of the immune response against heterogeneous hyperproliferative cells relative to a control nucleic acid molecule free of a neoantigen-encoding sequence.
Platform advantages including rapid manufacture, room-temperature stability, lower cost, reduction of immune escape, and avoidance of individual epitope validation.
Documented Applications
Treatment of cancer in a subject having cancer using a nucleic acid molecule encoding a concatemer of cancer neoantigens or antigenic determinants.
Enhancement of an immune response against heterogeneous hyperproliferative cells expressing neoantigens or antigenic determinants included in the chimeric polypeptide.
Use in combination with checkpoint inhibitors or immunostimulatory agents.
Evaluation in TC1, B16, CT26, LLC, and ID8 tumor models, ex-vivo dendritic-cell priming, and assessment of target-cell killing and tumor volume outcomes.
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