Lymphatic zip codes in tumors and pre-malignant lesions
View Patent ↗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 CLSDGK (SEQ ID NO:2), wherein the peptide selectively binds to tumor lymphatics.
2. The isolated peptide of claim 1 , wherein the peptide has a length of up to 25 amino acids.
3. The isolated peptide of claim 2 , wherein the peptide has a length of from 6 to 25 amino acids.
4. A conjugate comprising the peptide of claim 1 , 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 skin 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 skin 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 skin cancer in a subject, comprising administering to the subject in need thereof the conjugate of claim 5 , where the conjugate inhibits lymphangiogenesis in a tumor in the subject.
11. An isolated nucleic acid encoding the polypeptide of claim 1 .
12. The isolated nucleic acid of claim 11 further comprising a nucleic acid encoding a cellular internalization sequence.
13. The isolated nucleic acid of claim 12 , wherein the cellular internalization sequence is selected from the group consisting of Antennapedia, TAT, HIV-TAT, Penetratin, Antp-3A, Buforin, 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).