Cancer vaccines targeting Survivin and uses thereof
Inventors
Yan, Jian • SLAGER, Anna • GARMAN, Bradley • COOCH, Neil
Assignees
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Publication Number
US-12679904-B2
Publication Date
2026-07-14
Expiration Date
Abstract
Disclosed herein are nucleic acid molecules comprising one or more nucleic acid sequences that encode synthetic consensus Survivin antigens. Vectors, compositions, and vaccines comprising one or more nucleic acid sequences that encode synthetic consensus Survivin antigens are disclosed. Methods of treating a subject with a Survivin-expressing tumor and methods of preventing a Survivin-expressing tumor are disclosed. Synthetic consensus Survivin antigens are disclosed.
Core Innovation
The disclosure describes synthetic consensus Survivin nucleic acids and antigens, including Survivin isoform 1 and fused isoform 1T3 DNA constructs pGX1428 and pGX1429. These antigen constructs incorporate consensus design, codon and RNA optimization, an IgE leader, and mutations intended to abolish Survivin anti-apoptotic activity. The constructs and plasmid expression vectors express proteins that induce Survivin-specific IFN-γ and predominantly CD4+ T-cell responses.
Reported studies demonstrate immune responses in mice as well as vaccinated nonhuman primates, specifically rhesus macaques. Administering construct pGX1429 induces immune responses across animals, whereas adding interleukin-12 produces earlier, stronger, and more consistent responses. The disclosure further describes vaccines, plasmid vectors, and compositions for inducing immune responses against Survivin-expressing cancers.
Claims Coverage
The claims include six inventive features covering nucleic acid molecules, vectors, and compositions.
Nucleic acid molecules encoding modified Survivin proteins
Claim 1 covers a nucleic acid molecule comprising SEQ ID NO: 9 or SEQ ID NO: 10, or a sequence at least 95% identical to either specified sequence and encoding the referenced protein, comprising SEQ ID NO: 5 and alanine at positions 33, 47, and 83 of the corresponding referenced sequence.
Nucleic acid molecules encoding additional modified Survivin proteins
Claim 2 covers a nucleic acid molecule comprising SEQ ID NO: 1 or SEQ ID NO: 3, or a sequence at least 95% identical to either specified sequence and encoding the referenced protein, comprising SEQ ID NO: 5 and alanine at positions 51, 65, and 101 of the corresponding referenced sequence.
Nucleic acid molecule comprising a third specified sequence
Claim 3 covers a nucleic acid molecule comprising the recited nucleic acid sequence.
Nucleic acid molecule comprising a fourth specified sequence
Claim 4 covers a nucleic acid molecule comprising the recited nucleic acid sequence.
Vector comprising a Survivin nucleic acid molecule
Claim 5 covers a vector comprising a nucleic acid molecule selected from the specified sequence groups or qualifying sequence variants encoding the modified Survivin proteins.
Composition comprising Survivin nucleic acid molecules
Claim 7 covers a composition comprising one or more nucleic acid molecules selected from the specified sequence groups or qualifying sequence variants encoding the modified Survivin proteins.
The independent claims cover specified Survivin nucleic acid molecules and qualifying sequence variants, vectors containing the nucleic acids, and compositions comprising the nucleic acids.
Stated Advantages
The reported pGX1429 responses are earlier, stronger, and more consistent when IL-12 is added.
No significant immunization-related physiological changes are reported.
Documented Applications
Vaccines and compositions for inducing immune responses against Survivin-expressing cancers.
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