Isolation of a cell-specific internalizing peptide that infiltrates tumor tissue for targeted drug delivery

Abstract

The present invention provides a tumor-homing peptide that can target cancer and or tumor tissues. The peptide is uptaken by certain specific cancer cell types. The invention describes methods to achieve targeted delivery of anticancer drugs conjugated to this peptide for anticancer therapy. The invention also describes methods for using the peptide for the diagnosis and imaging of cancer and tumor tissues.

1 - 15 . (canceled)  
     
     
         16 . A method for killing a tumor cell comprising contacting said tumor cell with a pharmaceutically acceptable composition comprising: 
 a) a drug; and    b) a peptide that targets said tumor cell, wherein said peptide is internalized by said tumor cell.    
     
     
         17 . The method of  claim 16 , wherein said peptide comprises SEQ ID NO:1.  
     
     
         18 . The method of  claim 16 , wherein said drug is conjugated to said peptide.  
     
     
         19 . The method of  claim 16 , wherein said tumor cell is selected from the group consisting of squamous cell carcinoma, head and neck cancer and breast cancer.  
     
     
         20 . The method of  claim 16 , wherein said tumor cell is a human head and neck cancer cell.  
     
     
         21 . The method of  claim 16 , wherein said human head and neck cancer cell is an oral cavity cell, a pharynx cell, a throat cell, a paranasal sinus cell, a nasal cavity cell, a larynx cell, a thyroid cell, a parathyroid cell, a salivary gland cell, a skin cell of the face, a skin cell of the neck or a cervical lymph node cell.  
     
     
         22 . The method of  claim 16 , wherein said tumor cell is a solid tumor cell.  
     
     
         23 . The method of  claim 22 , wherein said solid tumor cell comprises a breast cancer cell.  
     
     
         24 . The method of  claim 16 , wherein said contacting is by intravenous administration, intratumoral administration, subcutaneous administration, intraperitoneal administration or topical administration.  
     
     
         25 . The method of  claim 16 , wherein said contacting is by local, regional or systemic administration.  
     
     
         26 . The method of  claim 16 , wherein said tumor cell is in a patient.  
     
     
         27 - 50 . (canceled)  
     
     
         51 . A method for killing a tumor cell comprising administering to a patient: 
 a) radiotherapy; and    b) a pharmaceutically acceptable composition comprising an anti-tumor compound conjugated to a peptide that targets said tumor cell, wherein said peptide is internalized by said tumor cell.    
     
     
         52 . The method of  claim 51 , wherein said peptide comprises SEQ ID NO:1.  
     
     
         53 . The method of  claim 51 , wherein said radiotherapy is administered whole body, local or regional.  
     
     
         54 . The method of  claim 51 , wherein said radiotherapy is radioisotopic irradiation, β-irradiation, X-ray irradiation, UV-irradiation, microwave irradiation or electronic irradiation.  
     
     
         55 . The method of  claim 51 , wherein said patient is administered about 40 to about 100 Gy radiation.  
     
     
         56 . The method of  claim 51 , wherein said patient is administered about 55 to about 65 Gy radiation.  
     
     
         57 . The method of  claim 51 , wherein said patient is administered about 62 Gy radiation.  
     
     
         58 . The method of  claim 51 , wherein said tumor cell is selected from the group consisting of squamous cell carcinomas, head and neck cancers and breast cancers.  
     
     
         59 . A method for killing a tumor cell comprising administering to a patient: 
 a) chemotherapy; and    b) a pharmaceutically acceptable composition comprising an anti-tumor compound conjugated to a peptide that targets said tumor cell, wherein said peptide is internalized by said tumor cell.    
     
     
         60 . A method for killing a tumor cell comprising administering to a patient: 
 a) chemotherapy; and    b) a pharmaceutically acceptable composition comprising a liposome linked to a peptide that targets said tumor cell, wherein said liposome comprises an anti-tumor compound, and wherein said peptide is internalized by said tumor cell.    
     
     
         61 . A method for killing a tumor cell comprising administering to a patient: 
 a) surgery; and    b) a pharmaceutically acceptable composition comprising an anti-tumor compound conjugated to a peptide that targets said tumor cell, wherein said peptide is internalized by said tumor cell.    
     
     
         62 . A method for killing a tumor cell comprising administering to a patient: 
 a) gene therapy; and    b) a pharmaceutically acceptable composition comprising an anti-tumor compound conjugated to a peptide that targets said tumor cell, wherein said peptide is internalized by said tumor cell.    
     
     
         63 . The method of  claim 62 , wherein said gene therapy is directed to a nucleic acid sequence selected from the group consisting of ras; myc, raf, erb, src, fms, jun, trk, ret, gsp, hst, bcl abl, Rb, CFTR, p16, p21, p27, p53, p57, p73, C-CAM, APC, CTS-1, zacl, scFV ras, DCC, NF-1, NF-2, WT-1, MEN-I, MEN-II, BRCA1, VHL, MMAC1, FCC, MCC, BRCA2, IL-1, IL-2, IL-3, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-11 IL-12, GM-CSF G-CSF and thymidine kinase.  
     
     
         64 - 83 . (canceled)  
     
     
         84 . A method for killing a cancer cell comprising the steps of: 
 (1) obtaining a peptide library;    (2) individually contacting peptides of said library with members of a cell population;    (3) assaying for endocytosis of said peptides by said members of said cell population to identify an internalizing peptide;    (4) conjugating a drug to said peptide; and    (5) administering the conjugated peptide and drug to an organism.    
     
     
         85 . A method for killing a cancer cell comprising the steps of: 
 (1) obtaining a peptide library;    (2) individually contacting peptides of said library with members of a cell population;    (3) assaying for endocytosis of said peptides by said members of said cell population to identify an internalizing peptide;    (4) conjugating a composition for gene therapy to said peptide; and    (5) administering the conjugated peptide and gene therapy composition to an organism.