Cancer Vaccines and Therapeutic Methods

Abstract

Compositions and methods of producing improved cancer vaccines are described. In addition, methods of identifying tumor associated antigens are also described.

1 . A composition comprising a chemotherapeutic agent and an antigen-presenting cell modified to express an allogeneic MHC-determinant, and wherein the cell has been transfected with genomic DNA or c-DNA isolated from the tumor of a mammal. 
     
     
         2 . The composition of  claim 1 , wherein the chemotherapeutic agent is selected from the group consisting of paclitaxel, docetaxel, vincristine, vinblastine, vinorelbine, irinotecan, topotecan, etoposide, methotrexate, 5-fluorouracil, cyclophosphamide, ifosphamide, melphalan, chlorambucil, BCNU, CCNU, decarbazine, procarbazine, busulfan, thiotepa, daunorubicin, doxorubicin, idarubicin, epirubicin, and mitoxantrone. 
     
     
         3 . The composition of  claim 1 , wherein the chemotherapeutic agent is paclitaxel. 
     
     
         4 . The composition of  claim 1 , wherein the antigen-presenting cell is further transfected with a nucleic acid molecule coding for at least one cytokine. 
     
     
         5 . The composition of  claim 4 , wherein the cytokine is selected from the group consisting of IL-2, granulocyte macrophage colony stimulating factor (GM-CSF), IL-4, IL-6, and IL-12. 
     
     
         6 . The composition of  claim 5 , wherein the cytokine is IL-2. 
     
     
         7 . The composition of  claim 1 , wherein the antigen-presenting cell is selected from the group consisting of a fibroblast, a macrophage, a B cell, and a dendritic cell. 
     
     
         8 . The composition of  claim 1 , wherein the tumor is a solid tumor or a hematological tumor. 
     
     
         9 . The composition of  claim 8 , wherein the tumor is selected from the group consisting of melanoma, lymphoma, plasmacytoma, sarcoma, glioma, thymoma, leukemias, breast cancer, prostate cancer, colon cancer, esophageal cancer, brain cancer, lung cancer, ovarian cancer, cervical cancer and hepatoma. 
     
     
         10 . The composition of  claim 1 , wherein the animal is a human subject. 
     
     
         11 . A method of treating a tumor in a mammal, comprising administering to the mammal a chemotherapeutic agent and an effective amount of an antigen-presenting cell modified to express an allogeneic MHC-determinant, and wherein the cell has been transfected with genomic DNA isolated from the tumor of the mammal. 
     
     
         12 . The method of  claim 1 , wherein the chemotherapeutic agent is selected from the group consisting of paclitaxel, docetaxel, vincristine, vinblastine, vinorelbine, irinotecan, topotecan, etoposide, methotrexate, 5-fluorouracil, cyclophosphamide, ifosphamide, melphalan, chlorambucil, BCNU, CCNU, decarbazine, procarbazine, busulfan, thiotepa, daunorubicin, doxorubicin, idarubicin, epirubicin, and mitoxantrone. 
     
     
         13 . The method of  claim 2 , wherein the chemotherapeutic agent is paclitaxel. 
     
     
         14 . The method of  claim 1 , wherein the antigen-presenting cell is further transfected with a nucleic acid molecule coding for at least one cytokine. 
     
     
         15 . The method of  claim 4 , wherein the cytokine is selected from the group consisting of IL-2, granulocyte macrophage colony stimulating factor (GM-CSF), IL-4, IL-6, and IL-12. 
     
     
         16 . The method of  claim 5 , wherein the cytokine is IL-2. 
     
     
         17 . The method of  claim 1 , wherein the antigen-presenting cell is selected from the group consisting of a fibroblast, a macrophage, a B cell, and a dendritic cell. 
     
     
         18 . The method of  claim 1 , wherein the tumor is a solid tumor or a hematological tumor. 
     
     
         19 . The method of  claim 8 , wherein the tumor is selected from the group consisting of melanoma, lymphoma, plasmacytoma, sarcoma, glioma, thymoma, leukemias, breast cancer, prostate cancer, colon cancer, esophageal cancer, brain cancer, lung cancer, ovarian cancer, cervical cancer and hepatoma. 
     
     
         20 . The method of  claim 1 , wherein the animal is a human subject. 
     
     
         21 . A method of treating a tumor in a mammal, comprising administering to the mammal a chemotherapeutic agent and an effective amount of an antigen-presenting cell that has been transfected with genomic DNA or c-DNA isolated from the tumor of the mammal. 
     
     
         22 . A method of enriching a population of immunogenic cells capable of inducing an immune response to a target cell in a patient, comprising:
 (a) providing a population of immunogenic cells capable of inducing an immune response to a target cell in a patient;   (b) incubating the immunogenic cells in growth medium;   (c) either before or after (b), diluting the suspension the immunogenic cells, whereby an enriched population of immunogenic cells is produced; and   (d) optionally repeating (a)-(c).   
     
     
         23 . The method of  claim 22  wherein said enriched population of immunogenic cells is polyclonal. 
     
     
         24 . The method of  claim 22  wherein said enriched population of immunogenic cells is monoclonal. 
     
     
         25 . The method of  claim 22  wherein said population of immunogenic cells are produced by a method comprising introducing DNA derived from said target cell into a recipient cell. 
     
     
         26 . The method of  claim 25  wherein the recipient cell is syngeneic, semi-allogeneic or allogeneic. 
     
     
         27 . The method of  claim 22  further comprising screening said enriched population of immunogenic cells for the ability to induce an immune response. 
     
     
         28 . The method of  claim 27  wherein said ability to induce an immune response is the in vitro or in vivo stimulation of T cells. 
     
     
         29 . A method of identifying a tumor associated antigen, comprising:
 (a) providing a recipient cell and an immunogenic cell capable of inducing an immune response to a tumor cell; and   (b) comparing the nucleic acid of the recipient cell and the immunogenic cell, whereby a nucleic acid with increased levels in the immunogenic cell encodes a tumor associated antigen.   
     
     
         30 . A method of identifying a tumor associated antigen, comprising:
 (a) providing a recipient cell and an immunogenic cell capable of inducing an immune response to a tumor cell; and   (b) comparing the expressed proteins of the immunogenic cell and the recipient cell, whereby a protein with increased expression in the immunogenic cell is a tumor associated antigen.   
     
     
         31 . A composition comprising an antigen-presenting cell modified to express an allogeneic MHC-determinant, and wherein the cell has been transfected with genomic DNA or c-DNA isolated from the tumor of a mammal. 
     
     
         32 . The composition of  claim 31 , wherein the antigen-presenting cell is further transfected with a nucleic acid molecule coding for at least one cytokine. 
     
     
         33 . The composition of  claim 31 , wherein the cytokine is selected from the group consisting of IL-2, granulocyte macrophage colony stimulating factor (GM-CSF), IL-4, IL-6, and IL-12. 
     
     
         34 . The composition of  claim 31 , wherein the cytokine is IL-2. 
     
     
         35 . The composition of  claim 31 , wherein the antigen-presenting cell is selected from the group consisting of a fibroblast, a macrophage, a B cell, and a dendritic cell. 
     
     
         36 . The composition of  claim 31 , wherein the tumor is a solid tumor or a hematological tumor. 
     
     
         37 . The composition of  claim 31 , wherein the tumor is selected from the group consisting of melanoma, lymphoma, plasmacytoma, sarcoma, glioma, thymoma, leukemias, breast cancer, prostate cancer, colon cancer, esophageal cancer, brain cancer, lung cancer, ovarian cancer, cervical cancer and hepatoma. 
     
     
         38 . The composition of  claim 31 , wherein the animal is a human subject.