Immunogenic compositions to the CCK-B/gastrin receptor and methods for the treatment of tumors

Abstract

The invention concerns immunogens, immunogenic compositions and method for the treatment of gastrin-dependent tumors. The immunogens comprise a peptide from the CCK-B/gastrin-receptor conjugated to a spacer and to an immunogenic carrier. The immunogens are capable of inducing antibodies in vivo which bind to the CCK-B/gastrin-receptor in tumor cells, thereby preventing growth stimulating peptide hormones from binding to the receptors, and inhibiting tumor cell growth. The immunogens also comprise antibodies against the CCK-B/gastrin-receptor for passive immunization. The invention also concerns diagnostic methods for detecting gastrin-dependent tumors in vivo or from a tissue biopsy using the antibodies of the invention.

We claim:  
     
         1 . An immunogen comprising a peptide from the CCK-B/gastrin-receptor conjugated to an Immunogenic carrier.  
     
     
         2 . The immunogen of  claim 1 , wherein the peptide has the amino acid sequence KLNRSVQGTGPGPGASL (SEQ ID NO.: 1 in the Sequence Listing) or GPGAHRALSGAPISF (SEQ ID NO.: 2 in the Sequence Listing).  
     
     
         3 . The immunogen of  claim 1  or  2 , further comprising a spacer peptide sequence.  
     
     
         4 . The immunogen of  claim 3 , wherein the spacer peptide sequence is SSPPPPC (SEQ ID NO.: 3 in the Sequence Listing).  
     
     
         5 . The immunogen of  claim 1 , wherein the immunogenic carrier is selected from the group consisting of Diphtheria toxoid, tetanus toxoid and bovine serum albumin.  
     
     
         6 . A method for treating a malignant condition caused by gastrin-dependent malignant cell growth comprising administering to an animal in need of such treatment an effective amount of an anti-CCK-B/gastrin-receptor immunogen.  
     
     
         7 . The method of  claim 6 , wherein the immunogen comprises a peptide from the CCK-B/gastrin-receptor.  
     
     
         8 . The method of  claim 7 , wherein the peptide has the amino acid sequence KLNRSVQGTGPGPGASL (SEQ ID NO.: 1 in the Sequence Listing) or GPGAHRALSGAPISF (SEQ ID NO.: 2 in the Sequence Listing).  
     
     
         9 . The method of  claim 8 , wherein the immunogen further comprises a spacer peptide sequence.  
     
     
         10 . The method of  claim 9 , wherein the spacer peptide sequence is SSPPPPC (SEQ ID NO.:3 in the Sequence Listing).  
     
     
         11 . The method of  claim 10 , further comprising an immunogenic carrier selected from the group consisting of Diptheria toxoid, tetanus toxoid and bovine serum albumin.  
     
     
         12 . A method for treating a gastrin-dependent tumor comprising administering to an animal in need of such treatment an effective amount of anti-CCK-B/gastrin antibodies which recognize and bind to the CCK-B/gastrin-receptors in the tumor cells.  
     
     
         13 . The method of  claim 12 , wherein the antibodies are selected from the group consisting of chimeric, monoclonal and humanized antibodies.  
     
     
         14 . The method of  claim 12 , wherein the anti-CCK-B/gastrin-receptor antibodies recognize and bind the amino acid sequence KLNRSVQGTGPGPGASL (SEQ ID NO.: 1 in the Sequence Listing) or GPGAHRALSGAPISF (SEQ ID NO.: 2 in the Sequence Listing) of the receptor.  
     
     
         15 . The method of  claim 12  or  14 , wherein the antibodies are further conjugated to a cytotoxic molecule.  
     
     
         16 . The method of  claim 15 , wherein the cytotoxic molecule is a toxin or a radioactive molecule.  
     
     
         17 . The method of  claim 16 , wherein the toxin is cholera toxin.  
     
     
         18 . The method of  claim 16 , wherein the radioactive molecule is labeled with  125 I or  131  I.  
     
     
         19 . A method for detecting a gastrin-responsive tumor containing CCK-B/gastrin-receptors, comprising exposing an anti-gastrin-receptor antibody to cells isolated from a tumor biopsy sample and detecting the CCK-B/gastrin-receptor in the sample.  
     
     
         20 . The method of  claim 19 , wherein the anti-gastrin-receptor antibody is specific for an amino-terminal peptide of the CCK-B/gastrin-receptor.  
     
     
         21 . The method of  claim 20 , wherein the peptide is in the amino-terminal region of the CCK-B/gastrin-receptor comprises amino acid residues 5-21.  
     
     
         22 . An immunogenic composition comprising an anti-CCK-B/gastrin-receptor immunogen.  
     
     
         23 . The composition of  claim 22 , wherein the immunogen comprises a peptide from the CCK-B/gastrin-receptor.  
     
     
         24 . The compostion of  claim 22 , wherein the immunogen comprises antibodies against the CCK-B/gastrin-receptor.  
     
     
         25 . A method for diagnosing a gastrin-dependent tumor, comprising administering radiolabeled anti-CCK-B/gastrin-receptor antibodies to a patient possessing a colorectal tumor and imaging the tumor by scintigraphic scanning.  
     
     
         26 . The method of  claim 25 , wherein the anti-CCK-B/gastrin-receptor antibodies are radiolabeled with  111 Indium or  90 Yttrium.