Muc18 targeting peptides

Abstract

Provided are MUC18 targeting peptides which may be used, e.g., to therapeutically target B-1 lymphocytes to reduce the influence of these cells on the metastatic potential of melanoma cells and/or to target cancerous cells, including certain melanoma and leukemia cells. MUC18 targeting peptides may be comprised in fusion constructs, imaging constructs, and/or therapeutic constructs such as fusion constructs which may be used for diagnosing or treating a cancer.

1 . An isolated peptide that selectively binds melanoma cell adhesion molecule (MUC18), wherein the isolated peptide comprises LFMRLAW (SEQ ID NO:22) or SEQ ID NO:2; and wherein if the peptide comprises SEQ ID NO:2, then the peptide is not MUC18. 
     
     
         2 . The isolated peptide of  claim 1 , wherein the isolated peptide further comprises SEQ ID NO:1. 
     
     
         3 . The isolated peptide of  claim 1 , wherein the peptide is from 6 to 35 amino acids in length. 
     
     
         4 . The isolated peptide of  claim 1 , wherein the peptide is from 7 to 15 amino acids in length. 
     
     
         5 . The isolated peptide of  claim 1 , wherein the isolated peptide is covalently coupled to a therapeutic agent. 
     
     
         6 . The isolated peptide of  claim 5 , wherein the therapeutic agent is a drug, a chemotherapeutic agent, a radioisotope, a pro-apoptosis agent, an anti-angiogenic agent, a hormone, a cytokine, a cytotoxic agent, a cytocidal agent, a cytostatic agent, a peptide, a protein, an antibiotic, an antibody, a Fab fragment of an antibody, a hormone antagonist, a nucleic acid or an antigen. 
     
     
         7 . The isolated peptide of  claim 6 , wherein the therapeutic agent is an anti-angiogenic agent, and wherein the anti-angiogenic agent is selected from the group consisting of thrombospondin, angiostatin, pigment epithelium-derived factor, angiotensin, laminin peptides, fibronectin peptides, plasminogen activator inhibitors, tissue metalloproteinase inhibitors, interferons, interleukin 12, platelet factor 4, IP-10, Gro-β, thrombospondin, 2-methoxyoestradiol, proliferin-related protein, carboxiamidotriazole, CM101, Marimastat, pentosan polysulphate, angiopoietin 2 (Regeneron), interferon-alpha, herbimycin A, PNU145156E, 16K prolactin fragment, Linomide, thalidomide, pentoxifylline, genistein, TNP-470, endostatin, paclitaxel, Docetaxel, polyamines, a proteasome inhibitor, a kinase inhibitor, a signaling peptide, accutin, cidofovir, vincristine, bleomycin, AGM-1470, platelet factor 4, and minocycline. 
     
     
         8 . The isolated peptide of  claim 6 , wherein the therapeutic agent is a pro-apoptosis agent, and wherein the pro-apoptosis agent is selected from the group consisting of etoposide, ceramide sphingomyelin, Bax, Bid, Bik, Bad, caspase-3, caspase-8, caspase-9, fas, fas ligand, fadd, fap-1, tradd, faf, rip, reaper, apoptin, interleukin-2 converting enzyme or annexin V. 
     
     
         9 . The isolated peptide of  claim 6 , wherein the therapeutic agent is a cytokine, and wherein the cytokine is selected from the group consisting of interleukin 1 (IL-1), IL-2, IL-5, IL-10, IL-12, IL-18, interferon-γ (IF-γ), IF α, IF-β, tumor necrosis factor-α (TNF-α), or GM-CSF (granulocyte macrophage colony stimulating factor). 
     
     
         10 . The isolated peptide of  claim 1 , wherein the peptide is attached to a molecular complex. 
     
     
         11 . The isolated peptide of  claim 10 , wherein the complex is a virus, a bacteriophage, a bacterium, a liposome, a microparticle, a magnetic bead, a yeast cell, a mammalian cell or a cell. 
     
     
         12 . The isolated peptide of  claim 11 , wherein the complex is a virus or a bacteriophage. 
     
     
         13 . The isolated peptide of  claim 12 , wherein the virus is chosen from the group consisting of adenovirus, retrovirus adeno-associated virus (AAV), and AAVP. 
     
     
         14 . The isolated peptide of  claim 12 , wherein the virus is further defined as containing a gene therapy vector. 
     
     
         15 . The isolated peptide of  claim 11 , wherein the peptide is attached to a eukaryotic expression vector. 
     
     
         16 . The isolated peptide of  claim 15 , wherein the vector is a gene therapy vector. 
     
     
         17 . The isolated peptide of  claim 1 , wherein the peptide is comprised in a pharmaceutically acceptable composition. 
     
     
         18 . A nucleic acid that encodes a protein or peptide comprising SEQ ID NO:22, SEQ ID NO:1 or SEQ ID NO:2, wherein if the nucleic acid comprises SEQ ID NO:2, then the protein or peptide is not MUC18. 
     
     
         19 . The nucleic acid of  claim 18 , wherein the nucleic acid is operably linked to a heterologous promoter. 
     
     
         20 .- 39 . (canceled)