HMGN2 peptides and related molecules that selectively home to tumor blood vessels and tumor cells
The present invention provides a conjugate which contains a therapeutic moiety linked to a homing molecule that selectively homes to tumor blood vessels and tumor cells and that specifically binds the receptor bound by peptide KDEPQRRSARLSAKPAPPKPEPKPKKAPAKK (SEQ ID NO: 9). Methods of directing a conjugate of the invention to tumor blood vessels and tumor cells and of using a conjugate to treat cancer also are provided.
1. A method of directing a therapeutic moiety to tumor blood vessels and tumor cells in a subject, comprising administering to the subject a conjugate which comprises a therapeutic moiety linked to a homing molecule that selectively homes to tumor blood vessels and tumor cells, said homing molecule specifically binding nucleolin, wherein the homing molecule is a peptide having a length of at most 200 amino acid residues comprising SEQ ID NO: 9 or SEQ ID NO: 11, thereby directing the therapeutic moiety to tumor blood vessels and tumor cells.
2. The method of claim 1 , wherein said homing molecule is not an antibody or antigen-binding fragment thereof.
3. The method of claim 1 , wherein the peptide portion of said conjugate has a length of at most 50 residues.
4. The method of claim 1 , wherein said therapeutic moiety is an anti-angiogenic agent.
5. The method of claim 1 , wherein said therapeutic moiety is a cytotoxic agent.
6. The method of claim 5 , wherein said cytotoxic agent is selected from the group consisting of an alkylating agent, and an anti-tumor antibiotic.
7. The method of claim 5 , wherein said cytotoxic agent is selected from the group consisting of cyclophosphamide, melphalan, mitomycin C, bizelesin, cisplatin, doxorubicin, etoposide, mitoxantrone, SN-38, Et-743, actinomycin D, bleomycin and TLK286.
8. A method of reducing the number of tumor blood vessels in a subject, comprising administering to the subject a conjugate which comprises a cytotoxic agent linked to a homing molecule that selectively homes to tumor blood vessels and tumor cells, said homing molecule specifically binding nucleolin, wherein the homing molecule is a peptide having a length of at most 200 amino acid residues comprising SEQ ID NO: 9 or SEQ ID NO: 11, thereby reducing the number of tumor blood vessels in said subject.