HER2DELTA16 peptides
View Patent ↗The present invention provides cyclic peptides comprising a dimer of peptides, each peptide comprising a sequence corresponding to the HER2 splice variant HER2Delta16, wherein the cyclic peptide is cyclized via a disulfide bond between the peptides and via an amino acid linking the peptides. The invention also provides methods of making antibodies that specifically bind to HER2Delta16 homodimers using said cyclic peptides.
1. An isolated antibody, or antigen-binding fragment thereof, that specifically binds to a HER2Δ16 cyclic peptide having the formula:
wherein each of X 1 and X 2 independently is selected from the group consisting of lysine, ornithine, β-amino-alanine, α,γ-diamino-butyric acid, and 2,7-diamino-heptanoic acid;
wherein each of Y 1 and Y 2 comprises a disulfide bond-forming compound, and wherein Y 1 is linked with Y 2 via a disulfide bond;
wherein the cysteine residues are linked via a disulfide bond; and
wherein X 1 and Thr are linked via a peptide bond.
2. The antibody of claim 1 , wherein each of X 1 and X 2 is a lysine.
3. The antibody of claim 1 , wherein each of Y 1 and Y 2 independently is selected from a cysteine residue or beta-mercaptopropionic acid.
4. The antibody of claim 1 , wherein the HER2416 cyclic peptide has the structure:
wherein MPA is beta-mercaptopropionic acid.
5. The antibody of claim 1 , wherein the antibody is a polyclonal antibody.
6. The antibody of claim 1 , wherein the antibody is a monoclonal antibody.
7. The antibody of claim 1 , wherein the antibody is a chimeric antibody.
8. The antibody of claim 1 , wherein the antibody is a humanized antibody.
9. The antibody of claim 1 , wherein the antigen-binding fragment is a Fab, a F(ab′) 2 , or a scFv.
10. The antibody of claim 1 , wherein the antibody is conjugated to a label.
11. The antibody of claim 10 , wherein the label is a fluorescent label or a radioactive label.
12. The antibody of claim 1 , wherein the antibody is conjugated to a therapeutic moiety.
13. The antibody of claim 12 , wherein the therapeutic moiety is an anti-cancer drug, a toxin, or a cytokine.
14. A pharmaceutical composition comprising the antibody of claim 1 and a pharmaceutically acceptable carrier.
15. A method of diagnosing a subject having a cancer that expresses HER2Δ16, the method comprising:
contacting a sample from the subject with an antibody that specifically binds to a a HER2Δ16 cyclic peptide having the formula:
wherein each of X 1 and X 2 independently is selected from the group consisting of lysine, ornithine, β-amino-alanine, α,γ-diamino-butyric acid, and 2,7-diamino-heptanoic acid; each of Y 1 and Y 2 comprises a disulfide bond-forming compound, and wherein Y 1 is linked with Y 2 via a disulfide bond; the cysteine residues are linked via a disulfide bond; and X 1 and Thr are linked via a peptide bond; and
detecting expression of HER2Δ16 in the sample; thereby diagnosing the subject as having a cancer that expresses HER2Δ16.
16. The method of claim 15 , wherein the sample is a tumor tissue sample.
17. The method of claim 15 , wherein the cancer is breast cancer.
18. The method of claim 15 , wherein the detecting step is performed using an enzyme immunoassay, a radioimmunoassay, or an immunohistochemical assay.
19. The method of claim 18 , wherein the detecting step is performed using an ELISA assay.
20. The method of claim 15 , wherein the method comprises determining the level of expression of HER2Δ16 in the sample.