Therapeutic cancer vaccine based on stress proteins rendered immunogenic

Abstract

The invention describes a method for preparing a composition comprising tumour cell stress proteins, said method comprising the following steps: providing tumour cells in a culture medium; subjecting the tumour cells under i) to a stress with the result that these cells produce stress proteins in response to the stress; obtaining or recovering stressed tumour cells and/or stress proteins; treating the stressed tumour cells and/or the stress proteins obtained with a molecule or a process capable of rendering the stress proteins immunogenic, preferably a hapten or haptenization. The invention also describes a pharmaceutical composition comprising tumour cell stress proteins and/or tumour cells comprising stress proteins, these stress proteins being rendered immunogenic, and are in particular haptenized, and a pharmaceutically acceptable excipient.

1 . Method for preparing a composition comprising stress proteins of tumour cells, which comprise the following steps:
 i) having tumour cells in a culture medium;   ii) subjecting in vitro the tumour cells under i) to a stress and ensuring the result that these cells produce stress proteins in response to the stress;   iii) obtaining or recovering stressed tumour cells and stress proteins;   iv) treating the stressed tumour cells and the stress proteins obtained in iii) with a molecule or a process capable of rendering the stress proteins immunogenic; with the tumour cells being inactivated after the steps ii), iii) or iv).   
     
     
         2 . The method according to  claim 1 , wherein, in step ii), the tumour cells are in the growth phase or in the plateau phase. 
     
     
         3 . The method according to  claim 1 , comprising a step iv) wherein the stressed tumour cells and/or stress proteins are submitted to haptenisation. 
     
     
         4 . The method according to  claim 3 , wherein the cells are incubated in vitro in the presence of a molecule selected from the group consisting of: Dinitrophenyl, 2,4-Dinitrofluorobenzene (DNFB), sulfanilic acid, N-iodoacetyl-N′(5-sulfonic-naphthyl) ethylene diamine (EDA), aniline, p-amino benzoic acid. 
     
     
         5 . The method according to  claim 1 , wherein the stress is selected from the group consisting of irradiation, heat shock, chemical shock and metabolic stress. 
     
     
         6 . The method according to  claim 1 , wherein the tumour cells in step i) comprise allogeneic cells from pre-established cell line, cells from original cell line of the patient, a combination of cells from pre-established allogeneic lines and/or cells from the patient, patient's cells or a combination of cells from allogeneic cell line and the patient's cells. 
     
     
         7 . (canceled) 
     
     
         8 . A pharmaceutical composition comprising immunogenic tumour cell stress proteins and/or non-proliferating tumour cells comprising immunogenic stress proteins, wherein the stress proteins have been induced on tumoral cells through in vitro stress selected from the group consisting of irradiation, heat, chemical and metabolic stress, and a pharmaceutically acceptable excipient. 
     
     
         9 . The composition according to  claim 7 , comprising non-proliferating tumour cells or fragments of such cells, bearing or containing haptenised stress proteins. 
     
     
         10 . The composition according to  claim 8 , comprising cells selected from the group consisting of cell line cells, a combination of cells from allogeneic cell lines, cells from the patient, and a combination of cells from allogeneic cell lines and patient's cells, these non-proliferative tumour cells bearing or containing haptenised stress proteins. 
     
     
         11 . The composition according to  claim 8 , comprising stress proteins selected from the group consisting of heat shock proteins, radioresistant proteins, chemotherapy resistant proteins, metabolic stress resistant proteins. 
     
     
         12 . The composition according to  claim 8 , further comprising an adjuvant. 
     
     
         13 . (canceled) 
     
     
         14 . An anti-cancer treatment method, comprising administering to a cancerous patient an effective amount of a composition comprising immunogenic tumour cell stress proteins and/or non-proliferating tumour cells comprising immunogenic stress proteins, wherein the stress proteins have been induced on tumoral cells through in vitro stress selected from the group consisting of irradiation, heat, chemical and metabolic stress, and a pharmaceutically acceptable excipient. 
     
     
         15 . The method according to  claim 14 , comprising administration of at least one dose of 10 5  to 10 7  tumour cells. 
     
     
         16 . The method according to  claim 14 , comprising 2, 3, 4, 5, 6, 7, 8, 9 or 10 administrations spaced out over an interval of 1 to 10 days between each administration. 
     
     
         17 . The composition of  claim 8 , wherein the stress proteins are haptenised. 
     
     
         18 . The method of  claim 14 , wherein the stress proteins are haptenised. 
     
     
         19 . The method according to  claim 14 , wherein the patient is treated with a conventional anti-cancer treatment protocol selected from the group consisting of surgery, radiation therapy, chemotherapy, immunotherapy and combinations thereof. 
     
     
         20 . The method according to  claim 14 , wherein the patient is treated with chemotherapy and the stress proteins have been induced through chemical stress. 
     
     
         21 . The method according to  claim 14 , wherein the patient is treated with chemotherapy with a chemotherapeutic agent and the stress proteins have been induced through chemical stress with the same chemotherapeutic agent. 
     
     
         22 . The method according to  claim 14 , wherein the patient is treated with radiation therapy and the stress proteins have been induced through irradiation stress. 
     
     
         23 . The method of  claim 14 , wherein administration of said composition comprising immunogenic tumour cell stress proteins and/or non-proliferating tumour cells comprising immunogenic stress proteins is performed in advance to a conventional anti-cancer treatment protocol selected from the group consisting of surgery, radiation therapy, chemotherapy, immunotherapy and combinations thereof.