Lm-1 antibodies, functional fragments, lm-1 target antigen, and methods for making and using same

Abstract

The invention provides LM-1 antibodies, functional fragments, modified and variant forms, nucleic acid and other compositions. The invention also provides antibodies, functional fragments, modified and variant forms that bind to LM-1 antigen (e.g., NONO/nmt55). Antibodies, functional fragments, modified and variant forms, nucleic acid and other compositions are useful in treatment and diagnostic methods. One method includes treating metastasis of a neoplasia, tumor or cancer in a subject in need of treatment by administering to the subject an amount of a LM-1 antibody, an antibody that binds to LM-1 antigen, or a functional fragment thereof, effective to treat metastasis of the neoplasia, tumor or cancer in the subject.

1 . An antibody or functional fragment thereof comprising a heavy and a light chain sequence variable region sequence with 60% or more identity to a heavy or light chain sequence variable region of antibody produced by a cell line DSMZ Deposit No. DSM ACC 2623. 
     
     
         2 . An antibody or functional fragment thereof, comprising heavy and light chain variable region sequences, wherein one or more of the CDRs in each of the heavy or light chain variable region sequences is at least 60% identical to a corresponding CDR of heavy or light chain sequences set forth in SEQ ID NO:1, 3, 5, 7 or 9, and 11 or 13. 
     
     
         3 . An antibody or functional fragment thereof comprising a heavy and a light chain sequence variable region sequence with a CDR comprising amino acids 24-35, 52-67, or 100-118 of SEQ ID NO:1, 3, 5 or 7, or amino acids 23-35, 51-58 or 90-101 of SEQ ID NO:11. 
     
     
         4 . The antibody or functional fragment of  claim 2 , wherein the CDR comprises a sequence that includes, consists of, or is within CDR1, VSGGSISSGGYY, CDR2, YIYYSGSTYYNPSLKS, and CDR3, VDARYDYVWGSYRYDAFDI of SEQ ID NO: 1, 3, 5 or 7, or CDR1, SGSSSNIGNNYVS, CDR2, DNNKRPSG, or CDR3, GTWDSSLSAGWV of SEQ ID NO:11. 
     
     
         5 . The antibody or functional fragment of  claim 1 , wherein the antibody or functional fragment thereof binds to NONO/nmt55 protein. 
     
     
         6 . An antibody or functional fragment thereof that competes with LM-1 antibody, produced by a cell line DSMZ Deposit No. DSM ACC 2623 for binding to NONO-nmt55. 
     
     
         7 . The antibody or functional fragment of  claim 6 , wherein the NONO-nmt55 comprises an N-terminal NONO-nmt55 amino acid sequence. 
     
     
         8 . The antibody or functional fragment of  claim 6 , wherein the NONO-nmt55 comprises a sequence set forth as: 
       
         
           
                 
                 
                 
               
                     1 
                   MQSNKTFNLE KQNHTPRKHH QHHHQQQHHQ QQQQQPPPPP IPANGQQASS 
                     
                 
                     
                 
                    51 
                   QNEGLTIDLK NFRKPGEKTF TQRSRLFVGN LPPDITEEEM RKLFEKYGKA 
                 
                     
                 
                   101 
                   GEVFIHKDKG FGFIRLETRT LAEIAKVELD NMPLRGKQLR VRFACHSASL 
                 
                     
                 
                   151 
                   TVRNLPQYVS NELLEEAFSV FGQVERAVVI VDDRGRPSGK GIVEFSGKPA 
                 
                     
                 
                   201 
                   ARKALDRCSE GSFLLTTFPR PVTVEPMDQL DDEEGLPEKL VIKNQQFHKE 
                 
                     
                 
                   251 
                   REQPPRFAQP GSFEYEYAMR WKALIEMEKQ QQDQVDRNIK EAREKLEMEM 
                 
             
                
                
                
                
                
                
                
                
                
                
                
               
            
           
         
       
     
     
         9 . An antibody or functional fragment thereof that binds to amino acids 1-300 of NONO-nmt55 sequence set forth as: 
       
         
           
                 
                 
                 
               
                     1 
                   MQSNKTFNLE KQNHTPRKHH QHHHQQQHHQ QQQQQPPPPP IPANGQQASS 
                     
                 
                     
                 
                    51 
                   QNEGLTIDLK NFRKPGEKTF TQRSRLFVGN LPPDITEEEM RKLFEKYGKA 
                 
                     
                 
                   101 
                   GEVFIHKDKG FGFIRLETRT LAEIAKVELD NMPLRGKQLR VRFACHSASL 
                 
                     
                 
                   151 
                   TVRNLPQYVS NELLEEAFSV FGQVERAVVI VDDRGRPSGK GIVEFSGKPA 
                 
                     
                 
                   201 
                   ARKALDRCSE GSFLLTTFPR PVTVEPMDQL DDEEGLPEKL VIKNQQFHKE 
                 
                     
                 
                   251 
                   REQPPRFAQP GSFEYEYAMR WKALIEMEKQ QQDQVDRNIK EAREKLEMEM 
                 
                     
                 
                   301 
                   EAARHEHQVM LMRQDLMRRQ EELRRMEELH NQEVQKRKQL ELRQEEERRR 
                 
                     
                 
                   351 
                   REEEMRRQQE EMMRRQQEGF KGTFPDAREQ EIRMGQMAMG GAMGINNRGA 
                 
                     
                 
                   401 
                   MPPAPVPAGT PAPPGPATMM PDGTLGLTPP TTERFGQAAT MEGIGAIGGT 
                 
                     
                 
                   451 
                   PPAFNRAAPG AEFAPNKRRR Y 
                 
             
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
               
            
           
         
       
     
     
         10 . An antibody or functional fragment thereof that competes for binding of LM-1 antibody to NONO/nmt55 protein, wherein the LM-1 antibody comprises SEQ ID NO:1, 3, 5, 7 or 9, and 11 or 13. 
     
     
         11 . The antibody or functional fragment of  claim 6 , wherein the NONO-nmt55 comprises a sequence set forth as: 
       
         
           
                 
                 
                 
               
                     1 
                   MQSNKTFNLE KQNHTPRKHH QHHHQQQHHQ QQQQQPPPPP IPANGQQASS 
                     
                 
                     
                 
                    51 
                   QNEGLTIDLK NFRKPGEKTF TQRSRLFVGN LPPDITEEEM RKLFEKYGKA 
                 
                     
                 
                   101 
                   GEVFIHKDKG FGFIRLETRT LAEIAKVELD NMPLRGKQLR VRFACHSASL 
                 
                     
                 
                   151 
                   TVRNLPQYVS NELLEEAFSV FGQVERAVVI VDDRGRPSGK GIVEFSGKPA 
                 
                     
                 
                   201 
                   ARKALDRCSE GSFLLTTFPR PVTVEPMDQL DDEEGLPEKL VIKNQQFHKE 
                 
                     
                 
                   251 
                   REQPPRFAQP GSFEYEYAMR WKALIEMEKQ QQDQVDRNIK EAREKLEMEM 
                 
             
                
                
                
                
                
                
                
                
                
                
                
               
            
           
         
       
     
     
         12 . The antibody or functional fragment of any  claim 6 , wherein the NONO/nmt55 protein is expressed on the surface of a cell. 
     
     
         13 . The antibody of  claim 6 , wherein the NONO/nmt55 protein comprises SEQ ID NO:16. 
     
     
         14 . The antibody or functional fragment of  claim 1 , wherein the antibody or functional fragment binds to Colo-699 (DSMZ accession number ACC 196), lung adenocarcinoma cell line DV-90 (DSMZ accession number ACC 307), epidermoid lung carcinoma cell line EPLC-272H (DSMZ accession number ACC 383), or lung squamous cell carcinoma cell line LOU-NH91 (DSMZ accession number ACC 393) cells. 
     
     
         15 . The antibody or functional fragment of  claim 1 , wherein the antibody or functional fragment competes with LM-1 antibody, produced by a cell line DSMZ Deposit No. DSM ACC 2623, or represented by heavy and light chain sequences set forth as SEQ ID NOs:1, 3, 5, 7 or 9, and 11 or 13 for binding to Colo-699 (DSMZ accession number ACC 196), lung adenocarcinoma cell line DV-90 (DSMZ accession number ACC 307), epidermoid lung carcinoma cell line EPLC-272H (DSMZ accession number ACC 383), or lung squamous cell carcinoma cell line LOU-NH91 (DSMZ accession number ACC 393) cells. 
     
     
         16 . The antibody or functional fragment of  claim 1 , wherein the antibody or functional fragment competes with LM-1 antibody, produced by a cell line DSMZ Deposit No. DSM ACC 2623, or represented by heavy and light chain sequences set forth as SEQ ID NOs:1, 3, 5, 7 or 9, and 11 or 13 for binding to NONO-nmt55. 
     
     
         17 . The antibody or functional fragment of  claim 1 , wherein the antibody or functional fragment competes with LM-1 antibody, produced by a cell line DSMZ Deposit No. DSM ACC 2623, or represented by heavy and light chain sequences set forth as SEQ ID NOs:1, 3, 5, 7 or 9, and 11 or 13 for binding to NONO-nmt55. 
     
     
         18 . The antibody or functional fragment of  claim 1 , wherein the antibody or functional fragment reduces or inhibits proliferation or growth of Colo-699 (DSMZ accession number ACC 196), lung adenocarcinoma cell line DV-90 (DSMZ accession number ACC 307), epidermoid lung carcinoma cell line EPLC-272H (DSMZ accession number ACC 383), or lung squamous cell carcinoma cell line LOU-NH91 (DSMZ accession number ACC 393) cells. 
     
     
         19 . The antibody or functional fragment of  claim 1 , wherein the antibody or functional fragment competes with LM-1 antibody, as represented by antibody produced by a cell line DSMZ Deposit No. DSM ACC 2623, for binding to a stomach adenocarcinoma (e.g., diffuse or intestinal), colorectal cancer such as adenocarcinoma, ovarian carcinoma, lung cancer, melanoma, lobular or ductal mammary carcinoma, breast cancer, gastric cancer, pancreatic cancer, sarcoma, gastrointestinal cancer, nervous tissue or brain tumor, esophageal cancer, osteosarcoma, fibrosarcoma, urinary bladder cancer, prostate cancer, kidney cancer, ovarian cancer, testicular cancer, endometrial cancer, cervical cancer, uterine cancer, Hodgkin's disease, lymphoma, or leukemia. 
     
     
         20 . The antibody or functional fragment of any of  claim 1 , wherein the antibody or functional fragment reduces, decreases or inhibits binding of LM-1 antibody, as represented by antibody produced by a cell line DSMZ Deposit No. DSM ACC 2623, to a stomach adenocarcinoma (e.g., diffuse or intestinal), colorectal cancer such as adenocarcinoma, ovarian carcinoma, lung cancer, melanoma, lobular or ductal mammary carcinoma, breast cancer, gastric cancer, pancreatic cancer, sarcoma, gastrointestinal cancer, nervous tissue or brain tumor, esophageal cancer, osteosarcoma, fibrosarcoma, urinary bladder cancer, prostate cancer, kidney cancer, ovarian cancer, testicular cancer, endometrial cancer, cervical cancer, uterine cancer, Hodgkin's disease, lymphoma, or leukemia. 
     
     
         21 . A nucleic acid that encodes the antibody or functional fragment of  claim 1 . 
     
     
         22 .- 25 . (canceled) 
     
     
         26 . A method for reducing or inhibiting growth, proliferation, mobility or invasiveness of neoplastic, tumor or cancer cells that can develop into or give rise to a metastasis in a subject in need of treatment, comprising administering to the subject an amount of an antibody or functional fragment thereof that competes with LM-1 antibody, produced by a cell line DSMZ Deposit No. DSM ACC 2623, or represented by heavy and light chain sequences set forth as SEQ ID NOs:1, 3, 5, 7 or 9, and 11 or 13 for binding to Colo-699 (DSMZ accession number ACC 196), lung adenocarcinoma cell line DV-90 (DSMZ accession number ACC 307), epidermoid lung carcinoma cell line EPLC-272H (DSMZ accession number ACC 383), or lung squamous cell carcinoma cell line LOU-NH91 (DSMZ accession number ACC 393) cells, effective to reduce or inhibit growth, proliferation, mobility or invasiveness of neoplastic, tumor or cancer cells that can develop into or give rise to the metastasis. 
     
     
         27 . A method for reducing or inhibiting neoplasia, tumor or cancer relapse, or neoplasia, tumor or cancer progression in a subject in need of treatment, comprising administering to the subject an amount of an antibody or functional fragment thereof that competes with LM-1 antibody, produced by a cell line DSMZ Deposit No. DSM ACC 2623, or represented by heavy and light chain sequences set forth as SEQ ID NOs:1, 3, 5, 7 or 9, and 11 or 13 for binding to Colo-699 (DSMZ accession number ACC 196), lung adenocarcinoma cell line DV-90 (DSMZ accession number ACC 307), epidermoid lung carcinoma cell line EPLC-272H (DSMZ accession number ACC 383), or lung squamous cell carcinoma cell line LOU-NH91 (DSMZ accession number ACC 393) cells, effective to reduce or inhibit neoplasia, tumor or cancer relapse, or neoplasia, tumor or cancer progression in the subject. 
     
     
         28 . A method for reducing or inhibiting growth or proliferation of a metastasis, after the metastasis has formed or has been established in a subject, comprising administering to the subject an amount of an antibody or functional fragment thereof that competes with LM-1 antibody, produced by a cell line DSMZ Deposit No. DSM ACC 2623, or represented by heavy and light chain sequences set forth as SEQ ID NOs:1, 3, 5, 7 or 9, and 11 or 13 for binding to Colo-699 (DSMZ accession number ACC 196), lung adenocarcinoma cell line DV-90 (DSMZ accession number ACC 307), epidermoid lung carcinoma cell line EPLC-272H (DSMZ accession number ACC 383), or lung squamous cell carcinoma cell line LOU-NH91 (DSMZ accession number ACC 393) cells, effective to reduce or inhibit growth or proliferation of the metastasis, after the metastasis has formed or has been established in the subject. 
     
     
         29 .- 45 . (canceled) 
     
     
         46 . A method for treating metastasis of a neoplasia, tumor or cancer in a subject in need of treatment, comprising administering to the subject an amount of an antibody or functional fragment comprising a heavy and a light chain sequence at least 70% identical to a heavy or light chain sequence set forth as SEQ ID NOs:1, 3, 5, 7, 9, 11 or 13 effective to treat metastasis of the neoplasia, tumor or cancer in the subject. 
     
     
         47 .- 73 . (canceled) 
     
     
         74 . A method for treating a neoplasia, tumor or cancer, or a metastasis thereof, in a subject in need of treatment, comprising administering to the subject an amount of an antibody or functional fragment thereof that binds to NONO-nmt55, effective to treat the neoplasia, tumor or cancer, or a metastasis thereof, in the subject. 
     
     
         75 .- 104 . (canceled) 
     
     
         105 . A method for detecting the presence of NONO/nmt55, or a cell expressing NONO/nmt55, comprising contacting a biological sample with the antibody of  claim 1  under conditions allowing binding of the antibody to NONO/nmt55 or a cell expressing NONO/nmt55, and assaying for binding to NONO/nmt55 or a cell expressing NONO/nmt55, wherein binding of the antibody to NONO/nmt55 or cell expressing NONO/nmt55 detects the presence of NONO/nmt55 or cell expressing NONO/nmt55 in the sample. 
     
     
         106 . A pharmaceutical formulation comprising NONO/nmt55. 
     
     
         107 . A vaccine comprising NONO/nmt55.