Use of biomolecular targets in the treatment and visualization of tumors

Abstract

The present invention relates to the use of a protein that is differentially expressed in primary brain tumor tissues, as compared to normal brain tissues, as a biomolecular target for tumor treatment therapies. The protein is also expressed in tissues from adenocarcinoma, non-melanoma, and renal carcinoma cells. Immunotherapeutic and immunoimaging agents that specifically bind to an identified brain tumor target protein are provided. The present invention also provides compounds and pharmaceutically acceptable compositions for administration in the methods of the invention.

1 . An isolated antibody, or antigen binding portion thereof, that binds to a TM7XN1 polypeptide comprising the amino acid sequence set forth in SEQ ID NO: 2. 
     
     
         2 . The antibody, or antigen binding portion thereof, of  claim 1 , wherein the antibody is a monoclonal antibody. 
     
     
         3 . The monoclonal antibody, or antigen binding portion thereof, of  claim 2 , wherein the monoclonal antibody is a human monoclonal antibody. 
     
     
         4 . An isolated antibody, or antigen binding portion thereof, that binds a TM7XN1 polypeptide, wherein the antibody modulates an activity of the TM7XN1 polypeptide. 
     
     
         5 . The antibody, or antigen binding portion thereof, of  claim 4 , wherein the antibody inhibits an activity of the TM7XN1 polypeptide. 
     
     
         6 . The antibody, or antigen binding portion thereof, of  claim 4 , wherein the antibody activates the TM7XN1 polypeptide. 
     
     
         7 . An isolated antibody, or antigen binding portion thereof, that binds a TM7XN1 polypeptide, wherein the antibody antagonizes ligand binding to the TM7XN1 polypeptide. 
     
     
         8 . The antibody, or antigen binding portion thereof, of  claim 1 , wherein the antibody is conjugated to one or more moieties. 
     
     
         9 . The antibody, or antigen binding portion thereof, of  claim 8  wherein the one or more moieties are cytotoxic or imaging moieties. 
     
     
         10 . The antibody, or antigen binding portion thereof, of  claim 9 , wherein the cytotoxic moieties are selected from the group consisting of a radioactive moiety, a chemotoxic moiety, and a toxin protein moiety. 
     
     
         11 . A composition comprising the antibody, or antigen-binding portion thereof, of  claim 1 , and a pharmaceutically acceptable carrier. 
     
     
         12 . A method of treating a brain tumor, renal carcinoma, adenocarcinoma or non-melanoma skin cancer expressing a TM7XN1 polypeptide, comprising administering to a patient in need of treatment a therapeutic amount of an agent that inhibits an activity of the TM7XN1 polypeptide such that treatment is achieved. 
     
     
         13 . The method of  claim 12 , wherein the agent is an antibody or antigen binding portion thereof. 
     
     
         14 . The method of  claim 13 , wherein the antibody, or antigen binding portion thereof, is human. 
     
     
         15 . The method of  claim 12 , wherein the agent is the antibody, or antigen binding portion thereof, of  claim 1 . 
     
     
         16 . The method of  claim 12 , wherein the agent is a small organic compound. 
     
     
         17 . The method of  claim 12 , wherein the agent binds to the extracellular domain of TM7XN1. 
     
     
         18 . The method of  claim 12 , wherein the agent is an RNAi or antisense agent. 
     
     
         19 . A method of treating a brain tumor, renal carcinoma, adenocarcinoma or non-melanoma skin cancer expressing a TM7XN1 polypeptide, comprising administering to a patient in need of treatment a therapeutic amount of an agent that specifically binds to the TM7XN1 polypeptide and, wherein the agent is conjugated to one or more cytotoxic moieties such that treatment is achieved. 
     
     
         20 . The method of  claim 19 , wherein the agent is an antibody or antigen binding portion thereof. 
     
     
         21 . The method of  claim 20 , wherein the antibody, or antigen binding portion thereof, is human. 
     
     
         22 . The method of  claim 19 , wherein the agent is the antibody, or antigen binding portion thereof, of  claim 1 . 
     
     
         23 . The method of  claim 19 , wherein the agent is a small organic compound. 
     
     
         24 . The method of  claim 19 , wherein the cytotoxic moiety is selected from the group consisting of a radioactive moiety, a chemotoxic moiety, and a toxin protein moiety. 
     
     
         25 . A method for inhibiting proliferation of a brain tumor cell, renal carcinoma cell, adenocarcinoma cell or non-melanoma skin cancer cell expressing a TM7XN1 polypeptide, comprising contacting the cell with an agent that inhibits an activity of the TM7XN1 polypeptide such that cell proliferation is inhibited. 
     
     
         26 . The method of  claim 25 , wherein the agent is an antibody or antigen binding portion thereof. 
     
     
         27 . The method of  claim 26 , wherein the antibody, or antigen binding portion thereof, is human. 
     
     
         28 . The method of  claim 25 , wherein the agent is the antibody, or antigen binding portion thereof, of  claim 1 . 
     
     
         29 . The method of  claim 25 , wherein the agent is a small organic compound. 
     
     
         30 . The method of  claim 25 , wherein the antibody specifically binds to the extracellular domain of TM7XN1. 
     
     
         31 . The method of  claim 25 , wherein the agent is an RNAi or antisense agent. 
     
     
         32 . A method for killing a brain tumor cell, renal carcinoma cell, adenocarcinoma cell or non-melanoma skin cancer cell expressing a TM7XN1 polypeptide, comprising contacting the cell with an agent that specifically binds to the TM7XN1 polypeptide and, wherein the agent is conjugated to one or more cytotoxic moieties such that cell killing is achieved. 
     
     
         33 . The method of  claim 32 , wherein the agent is an antibody or antigen binding portion thereof. 
     
     
         34 . The method of  claim 33 , wherein the antibody, or antigen binding portion thereof, is human. 
     
     
         35 . The method of  claim 32 , wherein the agent is the antibody, or antigen binding portion thereof, of  claim 1 . 
     
     
         36 . The method of  claim 32 , wherein the agent is a small organic compound. 
     
     
         37 . The method of  claim 32 , wherein the cytotoxic moiety is selected from the group consisting of a radioactive moiety, a chemotoxic moiety, and a toxin protein moiety.