Nucleolin Antibodies

Abstract

The present invention provides for methods of producing human monoclonal antibodies to human nucleolin, cells producing such antibodies, and the antibodies themselves. Also provided are methods of using the antibodies in diagnosing and treating malignant and non-malignant diseases wherein cells that express nucleolin on the cell surface contribute to the pathophysiology of the disease.

What is claimed is: 
     
         1 - 136 . (canceled) 
     
     
         137 . An anti-nucleolin agent, wherein the anti-nucleolin agent comprises an anti-nucleolin antibody, binds to amino acid sequence SEQ ID NO:4, and kills a diseased cell that overexpresses cell surface nucleolin or cytoplasmic nucleolin. 
     
     
         138 . The anti-nucleolin agent of  claim 137 , wherein the anti-nucleolin agent binds to the cell surface nucleolin. 
     
     
         139 . The anti-nucleolin agent of  claim 137 , wherein the anti-nucleolin agent binds to the cytoplasmic surface nucleolin. 
     
     
         140 . The anti-nucleolin agent of  claim 137 , wherein the anti-nucleolin agent binds to the cell surface nucleolin and the cytoplasmic surface nucleolin. 
     
     
         141 . The anti-nucleolin agent of  claim 137 , wherein the diseased cell is from a pulmonary fibrosis, macular degeneration, diabetic retinopathy, an inflammatory disease, an influenza virus, or a neurological symptom. 
     
     
         142 . The anti-nucleolin agent of  claim 137 , wherein the diseased cell is a cancer cell. 
     
     
         143 . The anti-nucleolin agent of  claim 142 , wherein the cancer cell is a lung cancer cell, a breast cancer cell, a prostate cancer cell, a colon cancer cell, a pancreatic cancer cell, a renal cell carcinoma cell, an ovarian cancer cell, a leukemia cell, a melanoma cell, a glioblastoma cell, a neuroblastoma cell, a sarcoma cell, or a gastric cancer cell. 
     
     
         144 . The anti-nucleolin agent of  claim 137 , wherein the anti-nucleolin agent induces apoptosis in a cancer cell. 
     
     
         145 . The anti-nucleolin agent of  claim 137 , wherein the anti-nucleolin agent kills a cancer cell in presence of human serum. 
     
     
         146 . The anti-nucleolin agent of  claim 137 , wherein the anti-nucleolin agent kills at least 50% of a population of MCF-7 cells, when incubated with the MCF-7 cells in presence of human AB serum for 48 hours or less. 
     
     
         147 . The anti-nucleolin agent of  claim 137 , wherein the anti-nucleolin agent kills more MCF-7 cells than MCF10A cells when incubated with separate populations of the MCF-7 cells and the MCF10A cells and heat inactivated serum for 96 hours or less. 
     
     
         148 . The anti-nucleolin agent of  claim 137 , wherein the anti-nucleolin agent is non-toxic to a normal cell. 
     
     
         149 . The anti-nucleolin agent of  claim 137 , wherein the anti-nucleolin agent further comprises a nanoparticle, a radionuclide, a fluorophore, a chemilluminescent compound, a fluorescent compound, an enzyme, a toxin, or a chemotherapeutic agent. 
     
     
         150 . The anti-nucleolin agent of  claim 149 , wherein the anti-nucleolin agent comprises the nanoparticle. 
     
     
         151 . The anti-nucleolin agent of  claim 150 , wherein the nanoparticle comprises nucleic acids. 
     
     
         152 . The anti-nucleolin agent of  claim 151 , wherein the nanoparticle is a DNA nanoparticle. 
     
     
         153 . The anti-nucleolin agent of  claim 137 , wherein the anti-nucleolin antibody is human. 
     
     
         154 . The anti-nucleolin agent of  claim 137 , wherein the anti-nucleolin antibody is humanized. 
     
     
         155 . The anti-nucleolin agent of  claim 137 , wherein the anti-nucleolin antibody is an IgG antibody. 
     
     
         156 . The anti-nucleolin agent of  claim 137 , wherein the anti-nucleolin antibody is an IgG1 antibody. 
     
     
         157 . A method of detecting a cell expressing cell surface or cytoplasmic nucleolin, comprising contacting the cell with an anti-nucleolin agent that comprises an anti-nucleolin antibody and binds to amino acid sequence SEQ ID NO:4.