Cancer vaccines targeting BORIS and uses thereof
Inventors
Yan, Jian • SLAGER, Anna • GARMAN, Bradley • COOCH, Neil
Assignees
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Publication Number
US-12161706-B2
Publication Date
2024-12-10
Expiration Date
Abstract
Disclosed herein are nucleic acid molecules comprising one or more nucleic acid sequences that encode a synthetic consensus BORIS antigen. Vectors, compositions, and vaccines comprising one or more nucleic acid sequences that encode a synthetic consensus BORIS antigen are disclosed. Methods of treating a subject with a BORIS-expressing tumor and methods of preventing a BORIS-expressing tumor are disclosed. A synthetic consensus BORIS antigen is disclosed.
Core Innovation
The invention relates to a cancer vaccine targeting BORIS (CTCFL) by providing nucleic acids encoding a non-native synthetic consensus BORIS antigen comprising a defined BORIS protein region. The synthetic consensus antigen includes amino acids 19-680 of SEQ ID NO:2 and is associated with an altered nuclear localization signal as described in the document.
The synthetic consensus BORIS antigen is defined by specific zinc-finger-disrupting mutations and a nuclear localization signal mutation. The zinc-finger-disrupting mutations are set out as C-to-G substitutions at positions including C276G, C279G, C304G, C307G, C332G, C335G, C361G, C364G, C389G, C392G, C417G, C420G, C447G, C450G, C477G, C480G, C505G, C508G, C533G, C536G, C565G, and C568G, together with K603R (RKRK→RRRK).
The vaccine is described as using nucleic acids and optionally plasmid or viral vector formats and protein antigen components intended for therapeutic and/or prophylactic use for BORIS-expressing tumors. The document further reports combinations with optional adjuvants and checkpoint-inhibitor blockade, and provides experimental examples showing construct generation, antigen expression confirmation, and immunogenicity including IFN-γ ELISpot responses and flow-cytometry profiles indicating predominantly CD8+ T-cell responses and cytolytic CD107a+ populations compared with empty-vector controls.
Claims Coverage
The independent claim defines a protein as a synthetic-consensus BORIS antigen region based on SEQ ID NO:2, with close-sequence variants permitted by specified sequence-identity and sequence-coverage thresholds while maintaining a defined set of zinc-finger-disrupting and nuclear localization mutations. The coverage is expressed through two alternative sequence-definition approaches tied to amino acids 19-680 of SEQ ID NO:2 and the mutation set, plus dependent refinements that narrow to broader sequence-identity definitions or the exact SEQ ID NO:2 sequence.
Protein comprising SEQ ID NO:2 amino acids 19-680 with defined C-to-G and K-to-R mutations
A protein comprising amino acids 19-680 of SEQ ID NO:2, and either (b) at least 90% of an entire length of amino acids 19-680 at 100% sequence identity to SEQ ID NO:2 with mutations C276G, C279G, C304G, C307G, C332G, C335G, C361G, C364G, C389G, C392G, C417G, C420G, C447G, C450G, C477G, C480G, C505G, C508G, C533G, C536G, C565G, C568G, and K603R of SEQ ID NO:2; or (c) an amino acid sequence at least 95% identical to amino acids 19-680 of SEQ ID NO:2 with the same mutation set; or (d) at least 90% of an entire length of an amino acid sequence that is at least 95% identical to amino acids 19-680 of SEQ ID NO:2 with the same mutation set.
Overall, the claim coverage centers on a BORIS synthetic-consensus antigen protein defined by SEQ ID NO:2 amino acids 19-680 together with the specified zinc-finger-disrupting C-to-G substitutions and the K603R nuclear localization signal mutation, with permitted homologous sequences defined by explicit identity and coverage thresholds; dependent claims further narrow the definition by anchoring to SEQ ID NO:2 as a whole or to the exact SEQ ID NO:2 amino acid sequence.
Stated Advantages
Not explicitly described in patent.
Documented Applications
Not explicitly described in patent.
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