Anti-tumor vaccine derived from normal cells

Abstract

A composition for inducing an immune response in a mammal, comprises lymphoid cells in which expression of tumor antigens has been chemically induced. The tumor antigens are induced in proliferating normal lymphoid cells, especially during the log phase of proliferation. The proliferation of the normal lymphoid cells is stimulated by normal mature dendritic cells. Most conveniently, the lymphoid cells are lymphocytes, especially peripheral blood lymphocytes. The tumor antigens are typically cancer/testis antigens, which may be chemically induced by DNA demethylation. Cancer/testis antigens are expressed in a wide range of tumors, so the composition is able to raise an immune response that is effective against a wide range of tumors, despite the fact that it is derived from normal cells. The composition may be used for preparation of an anti-tumor vaccine for prophylactic or therapeutic use. The composition may also be used for ex vivo activation of cytotoxic T lymphocytes, followed by expansion of the cytotoxic T lymphocyte population by normal dendritic cells, for cancer treatment by adoptive T cell immunotherapy.

1 - 5 . (canceled) 
     
     
         6 . A method of treating cancer by stimulating an immune response against tumors in a cancer patient in need thereof, comprising preparing an antigen-presenting composition enriched in CD4+ cells by a method comprising stimulating normal non-activated lymphoid cells to proliferate by co-culturing mature dendritic cells prepared from cultured blood monocytes, and chemically treating the proliferating cells with agents inducing DNA demethylation or histone acetylation to induce expression of cancer/testis antigens, and subsequently administering the antigen-presenting composition to the cancer patient to stimulate an immune response to the tumor antigens, wherein the antigen-presenting composition exhibits an increased ratio between CD4+ and CD8+ cells compared to the ratio between CD4+ and CD8+ cells in the normal non-activated lymphoid cells, and the mature dendritic cells are not loaded with the cancer/testis antigens. 
     
     
         7 . A method of reducing the risk of cancer in a subject, comprising preparing an antigen-presenting composition enriched in CD4+ cells by a method comprising stimulating normal non-activated lymphoid cells to proliferate by co-culturing with mature dendritic cells prepared from cultured blood monocytes, and chemically treating the proliferating cells with agents that induce DNA demethylation or histone acetylation to induce expression of cancer/testis antigens, and subsequently administering the antigen-presenting composition to the subject to stimulate an immune response to the cancer/testis antigens, wherein the antigen-presenting composition exhibits an increased ratio between CD4+ and CD8+ cells compared to the ratio between CD4+ and CD8+ cells in the normal non-activated lymphoid cells, and the mature dendritic cells are not loaded with the cancer/testis antigens. 
     
     
         8 . A method of treating cancer in a patient by adoptive T cell therapy, comprising preparing a cytotoxic composition by activating T cell lymphocytes with an antigen-presenting composition enriched in CD4+ cells, wherein said antigen-presenting composition is prepared by a method comprising stimulating normal non-activated lymphoid cells to proliferate by co-culturing with mature dendritic cells prepared from cultured blood monocytes, and chemically treating the proliferating cells with agents that induce DNA demethylation or histone acetylation to induce expression of cancer/testis antigens, and subsequently administering the cytotoxic composition to the patient, wherein the antigen-presenting composition exhibits an increased ratio between CD4+ and CD8+ cells compared to the ratio between CD4+ and CD8+ cells in the normal non-activated lymphoid cells, and the mature dendritic cells are not loaded with the cancer/testis antigens. 
     
     
         9 . A method of reducing the risk of cancer in a subject by adoptive T cell therapy, comprising preparing a cytotoxic composition by activating autologous T cell lymphocytes from the subject with an antigen-presenting composition enriched in CD4+ cells, the antigen-presenting composition being prepared by a method comprising stimulating normal non-activated lymphoid cells to proliferate by co-culturing with mature dendritic cells prepared from cultured blood monocytes, and chemically treating the proliferating cells with agents that induce DNA demethylation or histone acetylation to induce expression of cancer/testis antigens and subsequently administering the cytotoxic composition to the subject, wherein the antigen-presenting composition exhibits an increased ratio between CD4+ and CD8+ cells compared to the ratio between CD4+ and CD8+ cells in the normal non-activated lymphoid cells, and the mature dendritic cells are not loaded with the cancer/testis antigens. 
     
     
         10 . A composition for inducing an immune response in a mammal, comprising lymphoid cells in which expression of cancer/testis antigens has been chemically induced by DNA methylation or histone acetylation after activation with mature dendritic cells, wherein the lymphoid cells comprise an increased ratio between CD4+ and CD8+ cells compared to the ratio between CD4+ and CD8+ cells in autologous normal non-activated lymphoid cells in the mammal. 
     
     
         11 . A composition according to according to  claim 10 , in which the lymphoid cells are lymphocytes. 
     
     
         12 . A composition according to according to  claim 11 , in which the lymphocytes are peripheral blood lymphocytes. 
     
     
         13 - 16 . (canceled) 
     
     
         17 . A vaccine for prophylactic or therapeutic treatment comprising a composition according to  claim 10  and an acceptable carrier. 
     
     
         18 - 21 . (canceled) 
     
     
         22 . The method according to  claim 6 , in which the cancer/testis antigens have been induced during the log phase of proliferation. 
     
     
         23 . The method according to  claim 7 , in which the cancer/testis antigens have been induced during the log phase of proliferation. 
     
     
         24 . The method according to  claim 8 , in which the cancer/testis antigens have been induced during the log phase of proliferation. 
     
     
         25 . The method according to  claim 9 , in which the cancer/testis antigens have been induced during the log phase of proliferation. 
     
     
         26 . The method according to  claim 6 , wherein the normal non-activated lymphoid cells are autologous cells from the patient. 
     
     
         27 . The method according to  claim 7 , wherein the normal non-activated lymphoid cells are autologous cells from the subject. 
     
     
         28 . The method according to  claim 8 , wherein the normal non-activated lymphoid cells are autologous cells from the patient. 
     
     
         29 . The method according to  claim 9 , wherein the normal non-activated lymphoid cells are autologous cells from the subject. 
     
     
         30 . The method according to  claim 6 , wherein the normal non-activated lymphoid cells are heterologous cells. 
     
     
         31 . The method according to  claim 7 , wherein the normal non-activated lymphoid cells are heterologous cells. 
     
     
         32 . The method according to  claim 8 , wherein the normal non-activated lymphoid cells are heterologous cells. 
     
     
         33 . The method according to  claim 9 , wherein the normal non-activated lymphoid cells are heterologous cells. 
     
     
         34 . The method according to  claim 6 , wherein the dendritic cells are autologous cells prepared from cultured blood monocytes obtained from the patient. 
     
     
         35 . The method according to  claim 7 , wherein the dendritic cells are autologous cells prepared from cultured blood monocytes obtained from the subject. 
     
     
         36 . The method according to  claim 8 , wherein the dendritic cells are autologous cells prepared from cultured blood monocytes obtained from the patient. 
     
     
         37 . The method according to  claim 9 , wherein the dendritic cells are autologous cells prepared from cultured blood monocytes obtained from the subject. 
     
     
         38 . The method according to  claim 6 , wherein the dendritic cells are heterologous cells. 
     
     
         39 . The method according to  claim 7 , wherein the dendritic cells are heterologous cells. 
     
     
         40 . The method according to  claim 8 , wherein the dendritic cells are heterologous cells. 
     
     
         41 . The method according to  claim 9 , wherein the dendritic cells are heterologous cells. 
     
     
         42 . The method according to  claim 8 , in which the number of T cell lymphocytes is expanded after activation by use of mature dendritic cells. 
     
     
         43 . The method according to  claim 9 , in which the number of T cell lymphocytes is expanded after activation by use of mature dendritic cells. 
     
     
         44 . The method according to  claim 8 , wherein the T cell lymphocytes are autologous cells obtained from the patient. 
     
     
         45 . The method according to  claim 9 , wherein the T cell lymphocytes are autologous cells obtained from the subject. 
     
     
         46 . The method according to  claim 8 , wherein the T cell lymphocytes are heterologous cells. 
     
     
         47 . The method according to  claim 9 , wherein the T cell lymphocytes are heterologous cells.