Method for selecting tumours expressing HLA-G which are sensitive to anticancer treatment, and uses thereof

Abstract

The invention concerns a method for selecting tumours expressing HLA-G, sensitive to an anticancer treatment, which inhibits or prevents the HLA-G activity of said tumours and the uses thereof. Said method enable to establish either the HLA-G, transcription profile of a solid tumour or the HLA-G expression profile of a solid tumour. The method for establishing the HLA-G transcription profile consists in: (i) drawing a tumoral sample; (ii) extracting the mRNA; (iii) reverse transcription (RT) of said RNA: (iv) successive or simultaneous amplification of the cDNA's obtained in (iii) in the presence of primers specific to each HLA-G isoform and analysing the resulting amplification products, by electrophoresis and/or specific hybridisation and(v) establishing said sample HLA-G transcription profile. The method for establishing the HLA-G expression profile consists in: (i) drawing a tumoral sample; (ii) optionally marking said sample cells; (iii) carrying out a lysis of the cells; (iv) contacting said cells which have been subjected to lysis with different antibodies directed against the class I HLA-G antigens, to form, optionally HLA-G isform/antibodies complexes; and (v) establishing said sample HLA-G expression profile by detecting the complexes formed in step (iv).

1 - 13  (Canceled)  
     
     
         14 . A method of treating a solid tumor expressing at least one HLA-G isoform, comprising administering to a patient in need thereof, at least one substance selected from the group consisting of 
 autologous tumor cells expressing at least one HLA-G isoform;    a soluble HLA-G5 antigen;    a soluble HLA-G5 fragment;    an HLA-G antibody;    a factor which inhibits transcription of HLA-G; and    a factor which inhibits expression of HLA-G.    
     
     
         15 . The method of  claim 14 , wherein the autologous tumor cells are modified by a hyberbaric treatment or a cholesterol treatment.  
     
     
         16 . The method of  claim 14 , wherein the soluble HLA-G5 antigen or fragment thereof is coupled with an appropriate protein and optionally is associated with an adjuvant such as aluminum hydroxide or calcium phosphate.  
     
     
         17 . The method of  claim 14 , wherein the factor inhibiting the transcription and/or the expression of HLA-G is at least one member selected from the group consisting of antagonists for HL-G activating agents, antisense nucleic acids, and hormonal inhibitors for the transcription and/or the expression of the HLA-G.  
     
     
         18 . The method of  claim 14 , wherein the antagonists are selected from the group consisting of interleukin-10 antagonists, glucocorticoid antagonists, interferon antagonists, stress agent antagonists, and mixtures thereof.  
     
     
         19 . The method of  claim 14 , wherein the composition is administered subcutaneously or intradermally.  
     
     
         20 . The method of  claim 14 , wherein the anti-HLA-G antibody is administered as a combined product with a factor inhibiting the transcription and/or the expression of HLA-G.  
     
     
         21 . The method of  claim 20 , wherein the combined product is for simultaneous, separate, or staged use.  
     
     
         22 . An anti-tumor vaccine, comprising autlogous tumor cells expressing at least one HLA-G isoform.  
     
     
         23 . The anti-tumor vaccine of  claim 22 , wherein the autologous tumor cells are modified by a hyperbaric treatment or a cholesterol treatment.  
     
     
         24 . An anti-tumor vaccine, comprising at least one of a soluble HLA-G5 antigen or a fragment thereof.  
     
     
         25 . The anti-tumor vaccine of  claim 24 , wherein the soluble HLA-G antigen or fragment thereof is coupled with an appropriate protein.  
     
     
         26 . The anti-tumor vaccine of  claim 25 , which further comprise an adjuvant.  
     
     
         27 . The anti-tumor vaccine of  claim 26 , wherein the adjuvant is aluminum hydroxide, calcium phosphate, or mixtures thereof.  
     
     
         28 . A composition compring an anti-HLA-G antibody and a factor which inhibits the transcription and/or expression of HLA-G.  
     
     
         29 . The composition of  claim 28 , wherein the factor is selected from the group consisting of interleukin-10 antagonists, glucocorticoid antagonists, interferon antagonists, stress agent antagonists, and mixtures thereof.