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
CREAGRKAC (SEQ ID NO:6),
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 the peptide of claim 1 conjugated to a moiety, wherein the conjugate selectively homes to tumor lymphatics.
5. A conjugate comprising the peptide of claim 1 and a moiety 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, enzyme, biotin, metal, or epitope tag.
8. A method of detecting cancer in a subject, comprising administering to the subject the conjugate of claim 5 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 5 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 5 , 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 polypeptide of claim 1 .
14. The isolated nucleic acid of claim 13 further comprising a nucleic acid encoding a internalization sequence.
15. The isolated nucleic acid of claim 14 , wherein the cellular internalization comprises an amino acid sequence of a protein selected from a group consisting of Antennapedia, TAT, HIV-Tat, Penetratin, Antp-3A (Antp mutant), Buforin II, Transportan, MAP (model amphipathic peptide), K-FGF, Ku70, Prion, pVEC, Pep-1, SynB1, Pep-7, HN-1, BGSC (Bis-Guanidinium-Spermidine-Cholesterol and BGTC (Bis-Guanidinium-Tren-Cholesterol.
16. An expression vector comprising an isolated nucleic acid of claim 14 , wherein the nucleic acid is operably linked to an expression control sequence.