14-3-3 targeting peptides for cancer treatment
Inventors
Hansen, Laura • Lovas, Sandor • Palermo, Nicholas
Assignees
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Publication Number
US-12122852-B2
Publication Date
2024-10-22
Expiration Date
Abstract
Systems and methods for treatment of squamous cell carcinoma or other cancer utilizing targeting peptides are described. The targeting peptides interact with SCC cells or other cancerous cells to block or interfere with 14-3-3ε heterodimerization or CDC25A binding to 14-3-3ε. A peptide composition embodiment includes, but is not limited to, at least one of a first targeting peptide comprising a structure of Trp-Tyr-Trp-Lys-NH2 (SEQ ID NO: 1), a second targeting peptide comprising a structure of phospho-Ser178; Ac-Thr-Gln-Arg-Gln-Asn-Ser-(PO32−)-Ala-Pro-Arg-Met-Leu-Ser-Ser-Asn-NH2 (SEQ ID NO: 2), and a third targeting peptide comprising a structure of phospho-Thr507 residue; Ac-Arg-Thr-Lys-Ser-Arg-Thr(PO32−)-Trp-Ala-Gly-Glu-Lys-Ser-Lys-Arg-NH2 (SEQ ID NO: 3).
Core Innovation
The described invention relates to systems and methods for treating squamous cell carcinoma and other cancers using synthetic targeting peptides. The peptides are designed to disrupt 14-3-3ε function by blocking 14-3-3ε heterodimerization and/or preventing CDC25A binding to 14-3-3ε.
The disclosed peptide compositions include ES1P2 (Trp-Tyr-Trp-Lys-NH2; SEQ ID NO:1), the phospho-Ser178 CDC25A fragment peptide pS (SEQ ID NO:2), and the phospho-Thr507 CDC25A fragment peptide pT (SEQ ID NO:3). The patent content emphasizes that SEQ ID NO:3 corresponds to an isolated peptide having activity against squamous cell carcinoma survival.
The disclosure reports in vitro and in vivo results showing reduced SCC viability and increased apoptosis, together with decreased pro-survival signaling, including reduced P-Akt (S473) and Survivin. Mechanistic discussion is included showing disruption of 14-3-3ε interactions, including reduced heterodimerization and reduced CDC25A-14-3-3ε association, alongside discussion of selectivity versus normal keratinocytes and xenograft experiments.
Claims Coverage
The independent claim covers one inventive feature: an isolated peptide having activity against squamous cell carcinoma survival and defined by a specific sequence structure (SEQ ID NO: 3). The dependent claims add formulation features, including a pharmaceutically acceptable carrier, multiple administration routes, a water-immiscible solvent, and emulsion or topical-formulation types.
Isolated peptide for squamous cell carcinoma survival defined by SEQ ID NO: 3
An isolated peptide having activity against squamous cell carcinoma survival, the peptide comprising a structure as set forth in SEQ ID NO: 3.
Isolated peptide with pharmaceutically acceptable carrier
The isolated peptide comprises a pharmaceutically acceptable carrier.
Formulation with pharmaceutically acceptable carrier and specified administration routes
The isolated peptide is formulated with a pharmaceutically acceptable carrier suitable for administration by one or more specified routes including injection, topical, aerosol, inhalation, oral, systemic IV, ocular, and rectal delivery.
Carrier includes a water-immiscible solvent
The pharmaceutically acceptable carrier includes a water-immiscible solvent.
Emulsion and topical-formulation types
The isolated peptide includes one or more formulations chosen from an emulsion, lotion, cream, gel, or emollient.
Overall, the claims cover an isolated peptide (SEQ ID NO: 3) for squamous cell carcinoma survival, with formulation embodiments that add a pharmaceutically acceptable carrier, specify administration routes, and include emulsion, lotion, cream, gel, emollient, and water-immiscible solvent features.
Stated Advantages
Reduced SCC viability.
Increased apoptosis.
Decreased pro-survival signaling, including reduced P-Akt (S473) and Survivin.
Mechanistic disruption of 14-3-3ε interactions, including reduced 14-3-3ε heterodimerization and reduced CDC25A-14-3-3ε association.
Selectivity versus normal keratinocytes.
Documented Applications
Treatment of squamous cell carcinoma using synthetic targeting peptides that disrupt 14-3-3ε function via blocking 14-3-3ε heterodimerization and/or preventing CDC25A binding to 14-3-3ε, supported by in vitro and in vivo results including xenograft tumors.
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