Rapid production of autologous tumor vaccines

Abstract

An analogous vaccine to tumor cells is produced by transducing the tumor cells with a herpes simplex virus amplicon containing the gene for an immunomodulatory protein to provide transient expression of the immunomodulatory protein by the cells. The tumor cells may transduced with the herpes simplex amplicons ex vivo or in vivo. Suitable immunomodulatory proteins include cytokines, for example, interleukins, interferons, and chemokines such as RANTES; intercellular adhesion molecules, for example ICAM-1 and costimulatory factors such as B7.1. The tumor cells may also be transduced with one or more species of amplicon containing genes for two or more different immunomodulatory proteins.

1 . A method for production of an autologous vaccine to tumor cells comprising transducing the tumor cells with a herpes simplex virus amplicon containing the gene for an immunomodulatory protein to provide transient expression of the immunomodulatory protein by the cells.  
     
     
         2 . The method according to  claim 1 , wherein the tumor cells are transduced with the herpes simplex amplicons ex vivo.  
     
     
         3 . The method according to  claim 1 , wherein the tumor cells are transduced with the herpes simplex cell in vivo.  
     
     
         4 . The method according to  claim 1 , wherein the immunomodulatory protein is a cytokine.  
     
     
         5 . The method according to  claim 4 , wherein the cytokine is interleukin-2.  
     
     
         6 . The method according to  claim 4 , wherein the cytokine is granulocyte macrophage colony stimulating factor.  
     
     
         7 . The method according to  claim 4 , wherein the immunomodulatory protein is a chemokine.  
     
     
         8 . The method according to  claim 7 , wherein the chemokine is RANTES.  
     
     
         9 . The method according to  claim 1 , wherein the immunomodulatory protein is a intercellular adhesion molecule.  
     
     
         10 . The method according to  claim 9 , wherein the intracellular adhesion molecule is ICAM-1.  
     
     
         11 . The method according to  claim 1 , wherein the immunomodulatory protein is a costimulatory factor.  
     
     
         12 . The method according to  claim 11 , wherein the costimulatory factor is B7.1.  
     
     
         13 . The method according to  claim 1 , wherein a population of tumor cells is transduced with one or more species of amplicon containing the genes for more than one kind of immunomodulatory protein and expressing more than one kind of immunomodulatory protein.  
     
     
         14 . The method according to  claim 13 , wherein the tumor cells are transduced with amplicons encoding and expressing at least two species of cytokines.  
     
     
         15 . The method according to  claim 14 , wherein tumor cells are transduced with amplicons containing the genes for interleukin-2 and interleukin-12.  
     
     
         16 . The method according to  claim 13 , wherein the tumor cells are transduced with amplicons encoding and expressing a cytokine and a costimulatory factor.  
     
     
         17 . The method according to  claim 16 , wherein tumor cells are transduced with amplicons containing the genes for RANTES and B7.1.  
     
     
         18 . The method according to  claim 1 , wherein the tumor cells are hepatoma cells or lymphoma cells.  
     
     
         19 . A method for inducing a protective immune response to tumor cells in a patient comprising the step of transducing the tumor cells with a herpes simplex virus amplicon containing the gene for a immunomodulatory protein to provide transient expression of the immunomodulatory protein by the cells.  
     
     
         20 . The method according to  claim 19 , wherein the tumor cells are transduced with the amplicon ex vivo, further comprising the step of introducing the transduced tumor cells into the patient.  
     
     
         21 . The method according to  claim 19 , wherein the amplicons are injected into the site of the tumor cells in vivo.  
     
     
         22 . The method according to  claim 19 , wherein the immunomodulatory protein is a cytokine.  
     
     
         23 . The method according to  claim 22 , wherein the cytokine is interleukin-2.  
     
     
         24 . The method according to  claim 22 , wherein the cytokine is granulocyte macrophage colony stimulating factor.  
     
     
         25 . The method according to  claim 22 , wherein the immunomodulatory protein is a chemokine.  
     
     
         26 . The method according to  claim 25 , wherein the chemokine is RANTES.  
     
     
         27 . The method according to  claim 19 , wherein the immunomodulatory protein is a intercellular adhesion molecule.  
     
     
         28 . The method according to  claim 27 , wherein the intracellular adhesion molecule is ICAM-1.  
     
     
         29 . The method according to  claim 19 , wherein the immunomodulatory protein is a costimulatory factor.  
     
     
         30 . The method according to  claim 29 , wherein the costimulatory factor is B7.1.  
     
     
         31 . The method according to  claim 19 , wherein a population of tumor cells is transduced with one or more species of amplicon containing the genes for more than one kind of immunomodulatory protein and expressing more than one kind of immunomodulatory protein.  
     
     
         32 . The method according to  claim 31 , wherein the tumor cells are transduced with amplicons encoding and expressing at least two species of cytokines.  
     
     
         33 . The method according to  claim 32 , wherein tumor cells are transduced with amplicons containing the genes for interleukin-2 and interleukin-12.  
     
     
         34 . The method according to  claim 31 , wherein the tumor cells are transduced with amplicons encoding and expressing a cytokine and a costimulatory factor.  
     
     
         35 . The method according to  claim 34 , wherein tumor cells are transduced with amplicons containing the genes for RANTES and B7.1.  
     
     
         36 . The method according to  claim 19 , wherein the tumor cells are hepatoma cells or lymphoma cells.  
     
     
         37 . A herpes simplex virus amplicon containing the gene for at least one immunomodulatory protein.  
     
     
         38 . The amplicon according to  claim 37 , wherein the immunomodulatory protein is a cytokine.  
     
     
         39 . The amplicon according to  claim 38 , wherein the cytokine is interleukin-2.  
     
     
         40 . The amplicon according to  claim 38 , wherein the cytokine is granulocyte macrophage colony stimulating factor.  
     
     
         41 . The amplicon according to  claim 38 , wherein the immunomodulatory protein is a chemokine.  
     
     
         42 . The amplicon according to  claim 41 , wherein the chemokine is RANTES.  
     
     
         43 . The amplicon according to  claim 37 , wherein the immunomodulatory protein is a intercellular adhesion molecule.  
     
     
         44 . The amplicon according to  claim 43 , wherein the intracellular adhesion molecule is ICAM-1.  
     
     
         45 . The amplicon according to  claim 37 , wherein the immunomodulatory protein is a costimulatory factor.  
     
     
         46 . The amplicon according to  claim 45 , wherein the costimulatory factor is B7.1.  
     
     
         47 . The amplicon according to  claim 37 , wherein the amplicon contains genes encoding at least two immunomodulatory proteins.  
     
     
         48 . The amplicon according to  claim 47 , wherein the amplicon contains genes encoding for at least two species of cytokines.  
     
     
         49 . The amplicon according to  claim 48 , wherein the amplicon containing genes encoding for interleukin-2 and interleukin-12.  
     
     
         50 . Tumor cells transduced with a herpes simplex virus amplicon containing the gene for at least one immunomodulatory protein and expressing said immunomodulatory protein.  
     
     
         51 . The cells according to  claim 50 , wherein the immunomodulatory protein is a cytokine.  
     
     
         52 . The cells according to  claim 51 , wherein the cytokine is interleukin-2.  
     
     
         53 . The cells according to  claim 51 , wherein the cytokine is granulocyte macrophage colony stimulating factor.  
     
     
         54 . The cells according to  claim 51 , wherein the immunomodulatory protein is a chemokine.  
     
     
         55 . The cells according to  claim 54 , wherein the chemokine is RANTES.  
     
     
         56 . The cells according to  claim 50 , wherein the immunomodulatory protein is a intercellular adhesion molecule.  
     
     
         57 . The cells according to  claim 56 , wherein the intracellular adhesion molecule is ICAM-1.  
     
     
         58 . The cells according to  claim 50 , wherein the immunomodulatory protein is a costimulatory factor.  
     
     
         59 . The cells according to  claim 58 , wherein the costimulatory factor is B7.1.  
     
     
         60 . The cells according to  claim 50 , wherein the tumor cells are transduced with one or more species of amplicon containing the genes for more than one kind of immunomodulatory protein and expressing more than one kind of immunomodulatory protein.  
     
     
         61 . The cells according to  claim 60 , wherein the tumor cells are transduced with amplicons encoding and expressing at least two species of cytokines.  
     
     
         62 . The cells according to  claim 61 , wherein tumor cells are transduced with amplicons containing the genes for interleukin-2 and interleukin-12.  
     
     
         63 . The cells according to  claim 60 , wherein the tumor cells are transduced with amplicons encoding and expressing a cytokine and a costimulatory factor.  
     
     
         64 . The cells according to  claim 63 , wherein tumor cells are transduced with amplicons containing the genes for RANTES and B7.1.  
     
     
         65 . The cells according to  claim 50 , wherein the tumor cells are hepatoma cells or lymphoma cells.  
     
     
         66 . A method for production of an autologous vaccine to tumor cells comprising transducing the tumor cells with one or more species herpes simplex virus amplicon containing the gene for an immunomodulatory protein and at least one additional therapeutic gene to provide transient expression of the immunomodulatory protein and the therapeutic gene product by the cells.  
     
     
         67 . The method according to  claim 66 , wherein the tumor cells are transduced with the herpes simplex amplicons ex vivo.  
     
     
         68 . The method according to  claim 66 , wherein the tumor cells are transduced with the herpes simplex cell in vivo.  
     
     
         69 . A method for inducing a protective immune response to tumor cells in a patient comprising the step of transducing the tumor cells with one or more species herpes simplex virus amplicon containing the gene for an immunomodulatory protein and at least one additional therapeutic gene to provide transient expression of the immunomodulatory protein and the therapeutic gene product by the cells.  
     
     
         70 . A mixture containing a plurality of species of herpes simplex virus amplicons, including at least a first species of amplicon containing the gene for at least one immunomodulatory protein and a second species of amplicon containing the gene for an additional therapeutic gene product.