Cancer-associated antigen related applications

Abstract

The present invention provides a novel cancer-associated antigen that can be used in the treatment and diagnosis of cancer. Further, the invention provides amino acid and nucleic acid sequence of the novel antigen, binding proteins, and immunoconjugates. The invention also relates to diagnostic and therapeutic methods and kits.

We claim: 
     
         1 . A binding protein that binds to a protein comprising an amino acid sequence of SEQ ID NO: 1, or a variant thereof. 
     
     
         2 . The binding protein of  claim 1 , wherein the binding protein is an antibody or an antibody fragment. 
     
     
         3 . The binding protein of  claim 2 , wherein the antibody fragment is selected from the group consisting of Fab, Fab′, F(ab′)2, scFv, dsFv, ds-scFv, dimers, minibodies, diabodies, multimers thereof, and bispecific antibody fragments. 
     
     
         4 . A composition comprising a binding protein of  claim 1  with a pharmaceutically acceptable excipient, carrier, buffer, or stabilizer. 
     
     
         5 . An immunoconjugate comprising a binding protein that binds to a protein comprising an amino acid sequence of SEQ ID NO: 1, attached to an effector molecule. 
     
     
         6 . The immunoconjugate of  claim 5 , wherein the binding protein is an antibody or an antibody fragment. 
     
     
         7 . The immunoconjugate of  claim 6 , wherein the antibody fragment is selected from the group consisting of Fab, Fab′, F(ab′)2, scFv, dsFv, ds-scFv, dimers, minibodies, diabodies, multimers thereof, and bispecific antibody fragments. 
     
     
         8 . The immunoconjugate of  claim 6 , wherein the antibody or the antibody fragment is humanized. 
     
     
         9 . The immunoconjugate of  claim 5 , wherein the effector molecule is selected from the group consisting of a toxin, an enzyme conjugate, a labeled derivative, a fluorophore, a chromophore, an imaging agent, and a metal ion. 
     
     
         10 . The immunoconjugate of  claim 5 , wherein the effector molecule is a modified bouganin. 
     
     
         11 . A composition comprising an immunoconjugate of  claim 5  and a pharmaceutically acceptable excipient, carrier, buffer, or stabilizer. 
     
     
         12 . A method of treating a cancer in a subject comprising administering a therapeutically amount of an agent that inhibits cancer-associated variant of mammalian scratch protein (SEQ ID NO: 1). 
     
     
         13 . The method of  claim 12 , wherein the agent is selected from the group consisting of a binding protein to the cancer-associated variant of mammalian scratch protein, an antisense nucleic acid targeting the mRNA of cancer-associated variant of mammalian scratch protein, a ribozyme molecule targeting the mRNA of the cancer-associated variant of mammalian scratch protein, a triple helix structure targeting the gene encoding the cancer-associated variant of mammalian scratch protein, and any combination thereof. 
     
     
         14 . The method of  claim 12 , wherein the agent is an antibody fragment that binds to the cancer-associated variant of mammalian scratch protein. 
     
     
         15 . The method of  claim 14 , wherein the antibody fragment is selected from the group consisting of Fab, Fab′, F(ab′)2, scFv, dsFv, ds-scFv, dimers, minibodies, diabodies, multimers thereof, and bispecific antibody fragments. 
     
     
         16 . The method of  claim 12 , wherein the cancer is selected from the group consisting of stomach cancer, colon cancer, prostate cancer, cervical cancer, uterine cancer, ovarian cancer, pancreatic cancer, kidney cancer, liver cancer, head and neck cancer, squamous cell carcinoma, gastrointestinal cancer, breast cancer, lung cancer, non-Hodgkin's lymphoma, multiple myeloma, leukemia, brain cancer, sarcoma, bladder cancer, pancreatic cancer, endometrial cancer, plasmacytoma, lymphoma, and melanoma. 
     
     
         17 . The method of  claim 12 , wherein the agent is administered from a route selected from the group consisting of subcutaneous, intradermal, intramuscular, intravenous, intraperitoneal, mucosal, and any combination thereof. 
     
     
         18 . The method of  claim 12 , wherein the agent is administered in a pharmaceutical composition. 
     
     
         19 . A method of treating a subject with cancer comprising inducing an immune response to cancer-associated variant of mammalian scratch protein in the subject. 
     
     
         20 . The method of  claim 19 , wherein inducing an immune response comprises administering an effective amount of an isolated cancer-associated variant of mammalian scratch protein or a fragment thereof to the subject. 
     
     
         21 . The method of  claim 20 , wherein the isolated cancer-associated variant of mammalian scratch protein or a fragment thereof is administered in a pharmaceutical composition. 
     
     
         22 . The method of  claim 20 , further comprising administering an anticancer agent in combination with the isolated cancer-associated variant of mammalian scratch protein or a fragment thereof. 
     
     
         23 . The method of  claim 19 , wherein inducing an immune response comprises administering an effective amount of a recombinant expression vector encoding the cancer-associated variant of mammalian scratch protein. 
     
     
         24 . A method of treating a subject with cancer comprising:
 isolating lymphocytes from the subject;   contacting the isolated lymphocytes with cancer-associated variant of mammalian scratch protein or a fragment thereof in vitro; and   re-introducing the lymphocytes back into the subject to mount an immune response against cancer cells expressing the cancer-associated variant of mammalian scratch protein.   
     
     
         25 . A cancer-associated variant of mammalian scratch protein that is expressed on the surface of cancer cells. 
     
     
         26 . A pharmaceutical composition comprising the cancer-associated variant of mammalian scratch protein of  claim 25  along with a suitable diluent or carrier.