Internalizing ErbB2 antibodies
View Patent ↗This invention provides novel erbB2-binding internalizing antibodies. The antibodies, designated F5 and C1, specifically bind to c-erbB2 antigen and, upon binding, are readily internalized into the cell bearing the c-erbB2 marker. Chimeric molecules comprising the F5 and/or C1 antibodies attached to one or more effector molecules are also provided.
1. A method of specifically delivering an effector molecule to a cell bearing a c-erbB2 receptor, said method comprising:
providing a chimeric molecule comprising said effector molecule attached to an internalizing antibody that specifically binds to the c-erbB2 receptor, wherein said antibody specifically binds to a c-erbB2 epitope as bound by F5 (as encoded by ATCC plasmid deposit designation PTA7843) or C1 (SEQ ID NO: 2); and,
contacting said cell bearing a c-erbB2 receptor with said chimeric molecule, whereby said chimeric molecule specifically binds to said cell, wherein said effector molecule is selected from the group consisting of a cytotoxin, a label, a radionuclide, a drug, a liposome, a ligand, and an antibody.
2. The method of claim 1 , wherein the internalizing antibody is an scFv.
3. The method of claim 1 , wherein the internalizing antibody has an affinity for the c-erbB2 epitope as bound by F5 that is less than 10 −6 M.
4. The method of claim 1 , further comprising providing the chimeric molecule in a pharmaceutical composition comprising a pharmaceutical excipient and the chimeric molecule.
5. The method of claim 4 , further comprising administering the pharmaceutical composition parenterally.
6. The method of claim 5 , further comprising injecting the pharmaceutical composition intravenously.
7. The method of claim 1 , wherein the liposome bears an external hydrophilic polymer.
8. The method of claim 7 , wherein the liposome contains a therapeutic composition.
9. The method of claim 8 , wherein the therapeutic composition comprises doxorubicin.
10. The method of claim 7 , wherein the hydrophilic polymer is polyethylene glycol.
11. A method of specifically delivering an effector molecule to a cell bearing a c-erbB2 receptor, said method comprising:
providing a chimeric molecule comprising said effector molecule attached to an internalizing antibody that specifically binds to the c-erbB2 receptor, wherein said antibody specifically binds to a c-erbB2 epitope as bound by F5 (as encoded by ATCC plasmid deposit designation PTA7843) or C1 (SEQ ID NO: 2); and,
contacting said cell bearing a c-erbB2 receptor with said chimeric molecule, whereby said chimeric molecule specifically binds to said cell, wherein said cell is a cancer cell.
12. The method of claim 11 , wherein said cancer cell is a breast cancer cell.
13. The method of claim 11 , wherein the cancer cell is a carcinoma cell.
14. The method of claim 11 , wherein the internalizing antibody has an affinity for the c-erbB2 epitope as bound by F5 that is less than 10 −6 M.
15. The method of claim 11 , further comprising providing the chimeric molecule in a pharmaceutical composition comprising a pharmaceutical excipient and the chimeric molecule.
16. The method of claim 15 , further comprising administering the pharmaceutical composition parenterally.
17. The method of claim 16 further comprising injecting the pharmaceutical composition is intravenously.
18. A method of specifically delivering an effector molecule to a cell bearing a c-erbB2 receptor, said method comprising:
providing a chimeric molecule comprising said effector molecule attached to an internalizing antibody that specifically binds to the c-erbB2 receptor, wherein said antibody specifically binds to a c-erbB2 epitope as bound by F5 (as encoded by ATCC plasmid deposit designation PTA7843) or C1 (SEQ ID NO: 2); and
contacting said cell bearing a c-erbB2 receptor with said chimeric molecule, whereby said chimeric molecule specifically binds to said cell, wherein said chimeric molecule is a fusion protein.
19. A method of specifically delivering an effector molecule to a cell bearing a c-erbB2 receptor, said method comprising:
providing a chimeric molecule comprising said effector molecule attached to an internalizing antibody that specifically binds to said c-erbB2 receptor, wherein said internalizing antibody specifically binds to a c-erbB2 epitope as bound by F5 (as encoded by ATCC plasmid deposit designation PTA7843) or C1 (SEQ ID NO: 2), and wherein said internalizing antibody has a binding affinity for c-erbB2, on cells, of less than 10 −6 M; and,
contacting said cell bearing said c-erbB2 receptor with said chimeric molecule, whereby said chimeric molecule specifically binds to said cell.