Lymphatic zip codes in tumors and pre-malignant lesions
Disclosed herein are compositions and methods for and involving selectively targeting tumor lymphatics.
1. An isolated peptide having a length of up to 50 amino acids comprising CNRRTKAGC (SEQ ID NO: 17), wherein the peptide selectively binds to tumor lymphatics.
2. The peptide of claim 1 , wherein the peptide has a length of up to 25 amino acids.
3. The peptide of claim 2 , wherein the peptide has a length of from 9 to 25 amino acids.
4. A conjugate comprising an isolated peptide having a length of up to 50 amino acids comprising CNRRTKAGC (SEQ ID NO: 17) conjugated to a moiety, wherein the conjugate selectively homes to tumor lymphatics.
5. The conjugate of claim 4 , wherein the moiety is selected from the group consisting of a therapeutic moiety, a detectable moiety, a cytotoxic agent, an anti-lymphangiogenic agent, a cancer chemotherapeutic agent, a pro-apoptotic polypeptide, a grafted polypeptide, a virus, a cell, and a liposome, wherein the conjugate selectively homes to tumor lymphatics.
6. The conjugate of claim 5 , wherein the moiety is a cytotoxic agent, wherein the cytotoxic agent is D (KLAKLAK) 2 (SEQ ID NO: 19).
7. The conjugate of claim 5 , wherein the moiety is a detection moiety selected from a fluorophore, an enzyme, biotin, a metal, or an epitope tag.
8. A method of detecting cancer in a subject, comprising administering to the subject the conjugate of claim 4 conjugated to a detectable moiety and detecting the presence of the conjugate in the lymphatics of the subject, wherein detecting the presence of more of the conjugate in the lymphatics than a reference or control amount indicates the presence of cancer.
9. A method of detecting cancer, comprising contacting a biological sample with the conjugate of claim 4 conjugated to a detectable moiety and detecting the presence of the conjugate in the lymphatics of the sample, wherein detecting the presence of more of the conjugate in the lymphatics than a reference or control amount indicates the presence of cancer.
10. A method of treating prostate cancer in a subject, comprising administering to the subject the conjugate of claim 4 conjugated to a therapeutic moiety, wherein the conjugate inhibits lymphangiogenesis in a tumor in the subject.
11. The method of claim 10 , wherein the prostate cancer is malignant prostate cancer.
12. A method of determining malignant prostate conditions in a subject, comprising contacting a biological sample from the subject with a conjugate according to claim 4 .
13. An isolated nucleic acid encoding the isolated peptide of claim 1 .
14. An isolated nucleic acid encoding a peptide having a length of up to 50 amino acids comprising CNRRTKAGC (SEQ ID NO: 17), and further comprising a second nucleic acid encoding a cellular internalization sequence.
15. The isolated nucleic acid of claim 14 , wherein the cellular internalization sequence comprises an amino acid sequence of a protein selected from a group consisting of Antennapedia (SEQ ID NO: 44), HIV-Tat (SEQ ID NO: 45), Penetratin (SEQ ID NO: 46), Antp mutant Antp-3A (SEQ ID NO: 47), Tat (SEQ ID NO: 48), Buforin II (SEQ ID NO: 49), Transportan (SEQ ID NO: 50), model amphipathic peptide (MAP; SEQ ID NO: 51), K-FGF (SEQ ID NO: 52), Ku70 (SEQ ID NO: 53), Prion (SEQ ID NO: 54), pVEC (SEQ ID NO: 55), Pep-1 (SEQ ID NO: 56), SynB1 (SEQ ID NO: 57), Pep-7 (SEQ ID NO: 58), HN-1 (SEQ ID NO: 59), Bis-Guanidinium-Spermidine-Cholesterol (BGSC), and Bis-Guanidinium-Tren-Cholesterol (BGTC).
16. An expression vector comprising an isolated nucleic acid of claim 14 , wherein the nucleic acid is operably linked to an expression control sequence.