Peptides that home to tumor lymphatic vasculature and methods of using same
The present invention provides a conjugate containing a moiety linked to a homing molecule that selectively homes to tumor lymphatic vasculature. The invention also provides a method of directing a moiety to tumor lymphatic vasculature in a subject by administering to the subject a conjugate containing a moiety linked to a homing molecule that selectively homes to tumor lymphatic vasculature.
1. A conjugate, comprising a moiety linked to a homing molecule that selectively homes to tumor lymphatic vasculature, wherein said homing molecule is a peptide comprising the amino acid sequence GNKRTRG (SEQ ID NO: 2).
2. The conjugate of claim 1 , wherein said peptide is not an antibody or antigen-binding fragment thereof.
3. The conjugate of claim 1 , wherein the peptide portion of said conjugate has a length of at most 200 residues.
4. The conjugate of claim 3 , wherein the peptide portion of said conjugate has a length of at most 50 residues.
5. The conjugate of claim 1 , wherein said peptide is conformationally constrained.
6. The conjugate of claim 1 , wherein said peptide is cyclic.
7. The conjugate of claim 1 , wherein said homing molecule is a peptide comprising the amino acid sequence CGNKRTRGC (SEQ ID NO: 1).
8. The conjugate of claim 7 , wherein said homing molecule is conformationally constrained.
9. The conjugate of claim 7 , wherein said homing molecule is cyclic.
10. The conjugate of claim 1 , wherein said moiety is a therapeutic agent.
11. The conjugate of claim 1 , wherein said moiety is a cancer chemotherapeutic agent.
12. The conjugate of claim 1 , wherein said moiety is a cytotoxic agent.
13. The conjugate of claim 1 , wherein said moiety is an anti-lymphangiogenic agent.
14. The conjugate of claim 1 , wherein said moiety is a detectable label.
15. The conjugate of claim 1 , wherein said moiety is a phage.
16. The conjugate of claim 1 , comprising at least two homing molecules that each selectively homes to tumor lymphatic vasculature.
17. The conjugate of claim 16 , comprising at least ten homing molecules that each selectively homes to tumor lymphatic vasculature.
18. The conjugate of claim 17 , comprising at least 100 homing molecules that each selectively homes to tumor lymphatic vasculature.
19. The conjugate of claim 18 , wherein said moiety is a phage.
20. The conjugate of claim 1 , comprising at least two homing molecules that each selectively homes to tumor lymphatic vasculature, said homing molecules each independently comprising the amino acid sequence GNKRTRG (SEQ ID NO: 2).
21. The conjugate of claim 20 , comprising at least ten homing molecules that each selectively homes to tumor lymphatic vasculature, said homing molecules each independently comprising a peptide comprising the amino acid sequence GNKRTRG (SEQ ID NO: 2).
22. The conjugate of claim 21 , comprising at least 100 homing molecules that each selectively homes to tumor lymphatic vasculature, said homing molecules each independently comprising a peptide comprising the amino acid sequence GNKRTRG (SEQ ID NO: 2).
23. The conjugate of claim 22 , wherein said moiety is a phage.
24. The conjugate of claim 1 , wherein the peptide portion of said conjugate has a length of less than 20 residues.
25. The conjugate of claim 1 , wherein the peptide portion of said conjugate has a length of less than 15 residues.
26. The conjugate of claim 1 , wherein the peptide portion of said conjugate has a length of less than 12 residues.
27. The conjugate of claim 1 , wherein the peptide portion of said conjugate has a length of less than 10 residues.
28. The conjugate of claim 1 , wherein the peptide portion of said conjugate has a length of less than 9 residues.
29. The conjugate of claim 1 , wherein the peptide portion of said conjugate has a length of less than 8 residues.
30. The conjugate of claim 1 , wherein the peptide portion of said conjugate consists of the amino acid sequence GNKRTRG (SEQ ID NO: 2).
31. The conjugate of claim 7 , wherein the peptide portion of said conjugate has a length up to 200 residues.
32. The conjugate of claim 7 , wherein the peptide portion of said conjugate has a length up to 50 residues.
33. The conjugate of claim 7 , wherein the peptide portion of said conjugate has a length of less than 20 residues.
34. The conjugate of claim 7 , wherein the peptide portion of said conjugate has a length of less than 15 residues.
35. The conjugate of claim 7 , wherein the peptide portion of said conjugate has a length of less than 12 residues.
36. The conjugate of claim 7 , wherein the peptide portion of said conjugate has a length of less than 10 residues.
37. The conjugate of claim 21 , wherein the peptide portion of said conjugate consists of the amino acid sequence CGNKRTRGC (SEQ ID NO: 1).