Anti-Neovasculature Preparations for Cancer

Abstract

Disclosed herein are immunogenic compositions, methods of designing immunogenic compositions, methods of treatment using immunogenic compositions, methods of evaluating cell-mediated immunity resulting from immunogenic compositions, research models, and methods of making research models, all of which relate to targeting tumor vasculature.

1 . A method of treating non-prostatic neoplastic disease comprising the step of immunizing a mammal to induce a cellular immune response directed against an antigen differentially expressed by tumor-associated neovasculature, wherein the immunization comprises delivering a therapeutic vaccine comprising at least one immunogen corresponding to an antigen expressed by tumor-associated neovasculature to a mammal having a non-prostatic neoplastic disease, wherein said antigen is prostate specific membrane antigen (PSMA). 
     
     
         2 . The method of  claim 1 , further comprising the step of treating the mammal with an anti-tumor therapy active directly against cancerous cells. 
     
     
         3 . The method of  claim 2 , wherein the anti-tumor therapy comprises immunization against a tumor-associated antigen. 
     
     
         4 . The method of  claim 1 , wherein the cellular immune response comprises a CTL response. 
     
     
         5 . The method of  claim 1 , further comprising the step of detecting the cellular immune response. 
     
     
         6 . The method of  claim 5 , wherein the detecting step comprises detection of tumor growth inhibition, tumor size reduction, inhibition of tumor metastasis, or increase in life expectancy of the mammal. 
     
     
         7 . The method of  claim 5 , wherein the detecting step comprises an assay selected from the group consisting of a cytokine assay, a chromium release assay, an immunofluorescence assay, a cytotoxic T lymphocyte (CTL) assay, an Elispot assay, and observation of the health of the mammal. 
     
     
         8 . The method of  claim 1  wherein the vaccine is a therapeutic nucleic acid vaccine. 
     
     
         9 . The method of  claim 8 , wherein the immunogen comprises a nucleic acid capable of conferring expression of at least a portion of said antigen. 
     
     
         10 . The method of  claim 1  wherein the immunogen comprises a protein, or fragment thereof. 
     
     
         11 . The method of  claim 1  wherein the immunogen comprises or encodes at least one peptide derived from the sequence of said antigen. 
     
     
         12 . The method of  claim 11 , wherein the at least one peptide comprises a housekeeping epitope. 
     
     
         13 . The method of  claim 12 , wherein the at least one peptide is co-C-terminal with the housekeeping epitope. 
     
     
         14 . The method of  claim 13 , further comprising at least one additional peptide wherein the at least one additional peptide comprises an immune epitope. 
     
     
         15 . The method of  claim 1  further comprising immunizing the mammal to induce a cellular immune response directed against a second antigen associated with a tumor wherein the immunization comprises delivering a therapeutic vaccine comprising at least a first immunogen corresponding to PSMA and a second immunogen corresponding to the second antigen to a mammal having a non-prostatic neoplastic disease. 
     
     
         16 . A method of treating non-prostatic neoplastic disease comprising the steps of:
 selecting a patient in need of treatment for a non-prostatic neoplastic disease; and   delivering to said patient a first means for inducing a cellular immune response directed against a first antigen which is differentially expressed by tumor associated neovasculature, wherein the antigen is prostate specific membrane antigen (PSMA).   
     
     
         17 . The method of  claim 16  further comprising delivering a second means for inducing a cellular immune response directed against a second antigen which is associated with a tumor. 
     
     
         18 . The method of  claim 16  wherein the first means induces a cellular immune response directed against at least one housekeeping epitope derived from said first antigen. 
     
     
         19 . The method of  claim 18  further comprising a second means for inducing a cellular immune response directed against said first antigen, where in the second means induces a cellular immune response directed against at least one immune epitope derived from said first antigen. 
     
     
         20 . A therapeutic vaccine comprising a first immunogen corresponding to a first antigen differentially expressed by tumor-associated neovasculature and a second immunogen corresponding to a second antigen associated with a tumor, wherein the first antigen is prostate specific membrane antigen (PSMA), and wherein the vaccine can induce a cellular immune response. 
     
     
         21 . The therapeutic vaccine of  claim 20  comprising at least one housekeeping epitope derived from the antigen. 
     
     
         22 . The therapeutic vaccine of  claim 21  further comprising at least one immune epitope derived from the antigen. 
     
     
         23 . A therapeutic nucleic acid vaccine comprising a means for inducing a cellular immune response directed against an antigen differentially expressed by tumor associated neovasculature, wherein the antigen is prostate specific membrane antigen (PSMA), and wherein the vaccine can induce a cellular immune response, and a pharmaceutically acceptable buffer.