Vaccines against cytokines and growth factors derived from malignant tumours

Abstract

The invention concerns vaccines comprising as active principle an immunogen which is a cytokinetic factor or a cell regulating factor particularly transcriptional or another type of factor with immunosuppressive/apoptotic/angiogenic properties abnormally released in the extracellular (stromal) environment by cancer or stromal cells of malignant tumours, and a pharmaceutically acceptable carrier for inducing a systemic or mucosal immune response with secretory formation of class IgC or IgA neutralising antibodies directed against the native factor, or which is derived from such a factor and the use of said immunogen to obtain a medicine for use as anticancer drug.

1 . A vaccine characterized in that it contains, as active ingredient, an immunogen which is 
 a cytokinic factor or a particularly transcriptional cell regulation factor or another type of factor with immunosuppressive/apoptotic/angiogenic properties abnormally released in the extracellular (stromal) medium by the cancer cells or the stromal cells of malignant tumors, as well as a pharmaceutically acceptable excipient allowing the induction of an systemic or mucosal immune reaction with formation of neutralizing antibodies of IgG or secretory IgA class directed against the native factor,    or which is derived from such a factor,    with the exception of: 
 IL-6, a fragment of IL-6 or an analogue of IL-6 in a form producing non mucosal immunity and not conjugated to a carrier protein such as KLH,  
 a p53 epitope too short to be immunogenic and conjugated to a carrier protein such as KLH,  
 a composition of a p53 protein or p53 peptide, of IL 12 and an adjuvant.  
   
     
     
         2 . A vaccine according to  claim 1  characterized in that the immunogen derived from a cytokinic factor or from a particularly transcriptional cell regulation factor or from another type of factor with immunosuppressive/apoptotic/angiogenic properties abnormally produced by the cancerous or stromal cells of malignant tumors by chemical, physical treatment by genetic mutation, by adjuvant conditioning or is the product of a genetic vaccination (DNA vaccine) or is a proteinic or peptidic fragment of such factor or also is derived from such a proteinic or peptidic fragment.  
     
     
         3 . A vaccine according to  claim 1  or  2  characterized in that the immunogen derived from a cytokinic factor or from a particularly transcriptional cell regulation factor or from another type of factor with immunosuppressive/apoptotic/angiogenic properties abnormally produced by the cancerous or stromal cells of malignant tumors or of a proteinic or peptidic fragment of such a factor by conjugation to a carrier protein which is KLH.  
     
     
         4 . A vaccine according to  claim 1 ,  2  or  3  characterized in that the immunogen is chosen from TGFβ, IL-10, the p53 protein, VEGF, IL-6, IFNγ, IFNα, the Fas ligand and TNFα or is derived from them.  
     
     
         5 . A vaccine according to  claim 1 ,  2  or  3  characterized in that the immunogen is TGFβ or is derived from it.  
     
     
         6 . A vaccine according to  claim 1 ,  2  or  3  characterized in that the immunogen is IL-6 conjugated to a carrier protein which is KLH.  
     
     
         7 . A vaccine according to  claim 1 ,  2  or  3  characterized in that the immunogen is the p53 protein or is derived from it.  
     
     
         8 . A vaccine according to  claim 1 ,  2  or  3  characterized in that the immunogen is VEGF or is derived from it.  
     
     
         9 . A vaccine according to  claim 1 ,  2  or  3  characterized in that the immunogen is IL-10 or is derived from it.  
     
     
         10 . A vaccine according to  claim 1 ,  2  or  3  characterized in that the immunogen is IFNγ or IFNα or is derived from them.  
     
     
         11 . A vaccine according to  claim 1 ,  2  or  3  characterized in that the immunogen is TNFα or is derived from it.  
     
     
         12 . A vaccine according to one of  claims 1  to  11  characterized in that it contains, as active ingredient, an immunogen which is a mutant of the native factor or a fragment of the native factor.  
     
     
         13 . Use of an immunogen which is a cytokinic factor or which is derived from a cytokinic factor or a particularly transcriptional cell regulation factor or from another type of factor with immunosuppressive/apoptotic/angiogenic properties abnormally produced in the extracellular (stromal) medium by cancer or stromal cells of malignant tumors for obtaining a medicament intended for use as an anticancer medicament by a mechanism of reducing the effects, on the microenvironment of said cancerous or stromal cells of malignant tumors, of a cytokinic factor or of a particularly transcriptional cell regulation factor or of another type of factor with immunosuppressive/apoptotic/angiogenic properties abnormally produced by said cancer or stromal cells of malignant tumors.  
     
     
         14 . Use according to  claim 13 , characterized in that the immunogen is chosen from TGFβ, IL-10, the p53 protein, VEGF, IL-6, IFNγ, IFNα, the Fas ligand and TNFα or is derived from them.