Methods and compositions for inhibition of metastasis

Abstract

This invention generally relates to methods of producing an antibody phage population having affinity for a tumor cell target expressing a metastatic phenotype. The invention further relates to antibody compositions that specifically bind to a cell surface receptor on the metastatic cell.

1 . An isolated antibody which specifically binds to an activated αvβ3 integrin receptor which is differentially produced on a cell in a metastatic state compared to a similar, non-metastatic cell. 
     
     
         2 . (canceled) 
     
     
         3 . The antibody of  claim 1  comprising SEQ ID NO: 4. 
     
     
         4 . The antibody of  claim 1  comprising an R-G-D sequence in a complementary determining region (CDR). 
     
     
         5 . The antibody of  claim 4 , wherein the complementary determining region is CDR-H3. 
     
     
         6 . The antibody of  claim 1 , wherein said metastatic cell targets to a tissue selected from breast, brain, lung, liver, or bone. 
     
     
         7 . A pharmaceutical composition comprising said antibody of  claim 1 . 
     
     
         8 . An isolated antibody which specifically binds to an activated αvβ3 integrin receptor and does not bind to a non-activated αvβ3 integrin receptor. 
     
     
         9 . The antibody of  claim 8 , wherein the activated αvβ3 integrin receptor is differentially produced on a cell in a metastatic state compared to a similar, non-metastatic cell. 
     
     
         10 . The antibody of  claim 8 , wherein the antibody is a ligand mimetic. 
     
     
         11 . A method for treating a disease state in a mammal comprising administering to the mammal an isolated antibody which specifically binds to an activated αvβ3 integrin receptor which is differentially produced on a cell in a metastatic state as compared to a similar, non-metastatic cell. 
     
     
         12 . The method of  claim 11 , wherein the disease state is neoplastic disease, solid tumor, hematological malignancy, leukemia, colorectal cancer, benign or malignant breast cancer, uterine cancer, uterine leiomyomas, ovarian cancer, endometrial cancer, polycystic ovary syndrome, endometrial polyps, prostate cancer, prostatic hypertrophy, pituitary cancer, adenomyosis, adenocarcinomas, meningioma, melanoma, bone cancer, multiple myeloma, CNS cancer, glioma, or astroblastoma. 
     
     
         13 . The method of  claim 12 , wherein the neoplastic disease is tumor cell metastasis in said mammal. 
     
     
         14 . The method of  claim 13 , wherein the disease state is breast cancer metastasis in said mammal. 
     
     
         15 . The method of  claim 11 , wherein the antibody comprises SEQ ID NO: 4. 
     
     
         16 . An isolated Bc-12 polynucleotide comprising a nucleotide sequence that has at least 90% identity to SEQ ID NO: 1. 
     
     
         17 . An isolated polypeptide comprising an amino acid sequence that has at least 90% sequence identity to SEQ ID NO: 2 and shares a biological function with Bc-12 scFv polypeptide encoded by Bc-12 polynucleotide deposited as ATCC No. PTA-6303. 
     
     
         18 . A vector comprising the polynucleotide of  claim 16 . 
     
     
         19 . An expression vector comprising the polynucleotide of  claim 16  in which the nucleotide sequence of the polynucleotide is operatively linked with a regulatory sequence that controls expression of the polynucleotide in a host cell. 
     
     
         20 . A host cell comprising the polynucleotide of  claim 16 , or progeny of the cell. 
     
     
         21 . An isolated Bc-15 polynucleotide comprising a nucleotide sequence that has at least 90% identity to SEQ ID NO: 3. 
     
     
         22 . An isolated polypeptide comprising an amino acid sequence that has at least 90% sequence identity to SEQ ID NO: 4 and shares a biological function with Bc-15 scFv polypeptide encoded by Bc-15 polynucleotide deposited as ATCC No. PTA-6304. 
     
     
         23 . A vector comprising the polynucleotide of  claim 21 . 
     
     
         24 . An expression vector comprising the polynucleotide of  claim 21  in which the nucleotide sequence of the polynucleotide is operatively linked with a regulatory sequence that controls expression of the polynucleotide in a host cell. 
     
     
         25 . A host cell comprising the polynucleotide of  claim 21 , or progeny of the cell.