pH-triggered membrane peptide-mediated epitope tethering at cell surfaces
AssigneesUniversity of Rhode Island Board of Trustees, Yale University
InventorsYana K. Reshetnyak, Oleg A. Andreev, Anna Moshnikova, Donald M. Engelman
Life of this patent
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Abstract
The invention features methods and compositions for eliciting an anti-tumor response in a subject comprising administering to the subject a pHLIP● construct comprising an antibody recruiting molecule linked to one or more pHLIP● peptides by a non-cleavable linker compound. The construct increases the amount of the antibody recruiting molecule on the surface of a diseased cell.
Claims18
A composition comprising an epitope linked to one or more pH-triggered peptides by a non-cleavable linker compound, wherein the composition comprises the formula of Epitope-Linker-Peptide, wherein Epitope is an antibody recruiting molecule or immune cell recruiting molecule, wherein Linker is a linker or an extension of the pH-triggered peptide, wherein Peptide is a pH-triggered peptide comprising the sequence AXDDQNPWRAYLDLLFPTDTLLLDLLWA (SEQ ID NO:
- 18) or AXDQDNPWRAYLDLLFPTDTLLLDLLWA (SEQ ID NO:
- 495), wherein upper case “X” indicates any amino acid or an Azido-containing amino acid, wherein each is a covalent bond, and wherein Epitope is a hemagglutinin peptide (HA peptide) and comprises a length of less than 50 amino acids.
A composition comprising two antibody recruiting molecules linked to a pH-triggered peptide, wherein the composition comprises the formula of Epitope1-Linker-Peptide-Linker-Epitope1, wherein Epitope1 is an antibody recruiting molecule;
- wherein Linker is a PEG linker;
- wherein Peptide is a pH-triggered peptide comprising the sequence Ac-AKQNDDQNKPWRAYLDLLFPTDTLLLDLLWA (SEQ ID NO:
- 511);
- Ac-AKQNDNDNKPWRAYLDLLFPTDTLLLDLLWA (SEQ ID NO:
- 535);
- ACQNDDQNCPWRAYLDLLFPTDTLLLDLLWA (SEQ ID NO:
- 536);
- or ACQNDNDNCPWRAYLDLLFPTDTLLLDLLWA (SEQ ID NO:
- 505), wherein each-is a covalent bond, and wherein one or both of the Epitope1 is a hemagglutinin peptide (HA peptide) and comprises a length of less than 50 amino acids.
Dependencies are inferred from the claim text.