Antagonists for abdominal vasopressin v2 receptor and uses thereof

Abstract

Provided herein are antagonists or binding agents of an abnormal vasopressin receptor V 2 (e.g., AbnV 2 ), such as antibodies and antigen-binding portions thereof specific for the receptor, for identifying and targeting cancer cells expressing such abnormal vasopressin receptor V 2 . Additionally provided are methods of using said antagonists or binding agents, for example, to image cancer cells or in biological samples, or diagnose cancers, both in vivo and in vitro. The antagonists or binding agents may also be used for treating patients suffering from a cancer expressing the abnormal vasopressin receptor V 2 , such as small cell lung cancer (SCLC), breast cancer, or ovarian cancer.

1 . A method of treating a cancer, or killing cancer cells, or inhibiting the proliferation and/or growth of cancer cells, in a patient expressing an abnormal vasopressin receptor V 2 , said method comprising administering a therapeutically effective amount of a binding agent specific for the abnormal vasopressin receptor V 2  to the patient in need thereof, wherein the abnormal vasopressin receptor V 2  lacks a functional 7 th  transmembrane region of the wild-type vasopressin receptor V 2 , and has a C-terminus exposed on extracellular surface of cells of the cancer. 
     
     
         2 . The method of  claim 1 , wherein the abnormal vasopressin receptor V 2  is AbnV 2 , or comprises the most C-terminal six residues of SEQ ID NO: 1. 
     
     
         3 - 6 . (canceled) 
     
     
         7 . The method of  claim 1 , wherein the binding agent is an antibody or an antigen-binding portion thereof. 
     
     
         8 . The method of  claim 7 , wherein the antibody or antigen-binding portion thereof binds to the exposed C-terminus of the abnormal vasopressin receptor V 2 . 
     
     
         9 - 10 . (canceled) 
     
     
         11 . The method of  claim 1 , further comprising administering an effective amount of a pharmaceutical composition comprising a chemotherapeutic agent effective for treating the cancer. 
     
     
         12 - 20 . (canceled) 
     
     
         21 . The method of  claim 1 , wherein the antibody or antibody-binding portion thereof comprises a label. 
     
     
         22 . The method of  claim 21 , wherein the label is selected from the group consisting of a fluorescent label, a radiolabel, a toxin, a metal compound, and biotin. 
     
     
         23 - 25 . (canceled) 
     
     
         26 . The method of  claim 1 , further comprising administering a provasopressin-binding antibody, such as MAG-1, MAG-2, MAG-3, MAG-4, MAG-5, or an antigen-binding portion thereof. 
     
     
         27 . A method of killing a cancer cell expressing an abnormal vasopressin receptor V 2 , the method comprising contacting the cancer cell with a binding agent specific for the abnormal vasopressin receptor V 2 , wherein the abnormal vasopressin receptor V 2  lacks a functional 7 th  transmembrane region of the wild-type vasopressin receptor V 2 , and has a C-terminus exposed on extracellular surface of cells of the cancer. 
     
     
         28 . (canceled) 
     
     
         29 . A method of inhibiting the growth of a cancer cell expressing an abnormal vasopressin receptor V 2 , the method comprising contacting the cancer cell with a binding agent specific for the abnormal vasopressin receptor V 2 , wherein the abnormal vasopressin receptor V 2  lacks a functional 7 th  transmembrane region of the wild-type vasopressin receptor V 2 , and has a C-terminus exposed on extracellular surface of cells of the cancer. 
     
     
         30 - 32 . (canceled) 
     
     
         33 . A method of diagnosing the presence in a patient a cancer expressing an abnormal vasopressin receptor V 2 , the method comprising:
 a) obtaining a biological sample (such as a biopsy) from the patient;   b) if necessary, rendering the biological sample amenable to immunoassay;   c) contacting the sample with the an antibody or an antigen-binding portion thereof specific for the abnormal vasopressin receptor V 2 , under conditions that allow for binding of the antibody or antigen-binding portion to the abnormal vasopressin receptor V 2 ; and   d) determining if the cells of the sample expresses a significantly higher level of the abnormal vasopressin receptor V 2  compared to a control tissue;   
       wherein the patient is diagnosed to have the cancer expressing the abnormal vasopressin receptor V 2  if the cells of the sample express a significantly higher level of the abnormal vasopressin receptor V 2  compared to the control tissue. 
     
     
         34 - 37 . (canceled) 
     
     
         38 . A kit for screening a biological sample for a cancer expressing an abnormal vasopressin receptor V 2 , the kit comprising an antibody or an antigen-binding portion thereof specific for the abnormal vasopressin receptor V 2 , wherein the kit is labeled for use in detecting the cancer expressing the abnormal vasopressin receptor V 2 . 
     
     
         39 - 40 . (canceled) 
     
     
         41 . A method of detecting or imaging in a patient a tumor expressing an abnormal vasopressin receptor V 2 , the method comprising:
 a) administering to the patient an antibody or an antigen-binding portion thereof specific for the abnormal vasopressin receptor V 2 , wherein the antibody or antigen-binding portion thereof comprise a detectable label;   b) detecting the label; and,   c) determining the amount of the label in the patient compared to that of a control.   
     
     
         42 - 49 . (canceled) 
     
     
         50 . An isolated polypeptide comprising the most C-terminal six residues of SEQ ID NO: 1. 
     
     
         51 . The isolated polypeptide of  claim 50 , which is a fusion protein comprising the most C-terminal six residues of SEQ ID NO: 1 fused to a heterologous protein. 
     
     
         52 - 53 . (canceled) 
     
     
         54 . An isolated abnormal vasopressin receptor V 2  (AbnV 2 ), having a sequence of SEQ ID NO: 4. 
     
     
         55 . An isolated polynucleotide encoding the isolated polypeptide of  claim 50 . 
     
     
         56 . A vector comprising the polynucleotide of  claim 55 . 
     
     
         57 . A cell comprising the isolated polynucleotide of  claim 55 . 
     
     
         58 . A cell comprising the vector of  claim 56 .