Cell fusions and methods of making and using the same

Abstract

The invention is concerned with fusions of dendritic cells and antigen presenting cells. Also provided are methods of making and using these cell fusions, including methods of adoptive immunotherapy. The fusions according to the invention can also be used in methods for antigen discovery.

1 . A substantially pure cytotoxic population of educated, antigen-specific immune effector cells expanded in culture by contacting immune effector cells with hybrid cells wherein the immune effector cells are T lymphocytes, wherein said population comprises CD4 +  immune effector cells and cytotoxic CD8 +  immune effector cells, wherein said hybrid cells are generated by fusion between at least one mammalian dendritic cell and at least one mammalian tumor or cancer cell that expresses a cell-surface antigen, wherein the dendritic cell and the cancer or tumor cell are from the same mammalian species, wherein the dendritic cell can process and present antigens, and wherein at least half of the hybrid cells express, in an amount effective to stimulate an immune system, (a) a MHC class II molecule, (b) B7, and (c) the cell-surface antigen.  
     
     
         2 . The population according to  claim 1 , wherein the antigen-specific immune effector cells are genetically modified cells.  
     
     
         3 . The population according to  claim 1 , wherein the hybrid cells are genetically modified cells.  
     
     
         4 . The population according to  claim 2 , wherein the genetic modification comprises introduction of a polynucleotide.  
     
     
         5 . The population according to  claim 4 , wherein the polynucleotide encodes a peptide, a ribozyme or an antisense sequence.  
     
     
         6 . A substantially pure cytotoxic population of educated, antigen-specific immune effector cells produced by culturing immune effector cells with hybrid cells wherein the immune effector cells are T lymphocytes, wherein said population comprises CD4 +  immune effector cells and cytotoxic CD8 +  immune effector cells, wherein said hybrid cells are generated by fusion between at least one mammalian dendritic cell and at least one mammalian tumor or cancer cell that expresses a cell-surface antigen, wherein the dendritic cell and the cancer or tumor cell are from the same mammalian species, wherein the dendritic cell can process and present antigens, and wherein at least half of the hybrid cells express, in an amount effective to stimulate an immune system, (a) a MHC class II molecule, (b) B7, and (c) the cell-surface antigen.  
     
     
         7 . The population according to  claim 6 , wherein the antigen-specific immune effector cells are genetically modified cells.  
     
     
         8 . The population according to  claim 6 , wherein the hybrid cells are genetically modified cells.  
     
     
         9 . The population according to  claim 7 , wherein the genetic modification comprises introduction of a polynucleotide.  
     
     
         10 . The population according to  claim 9 , wherein the polynucleotide encodes a peptide, a ribozyme or an antisense sequence.  
     
     
         11 . The population according to  claim 6 , wherein the immune effector cells are naïve prior to culturing said immune effector cells with hybrid cells.  
     
     
         12 . The population according to  claim 6 , wherein the immune effector cells are educated prior to culturing said cytotoxic immune effector cells with hybrid cells.  
     
     
         13 . The population according to  claim 6 , wherein the immune effector cells are produced by culturing immune effector cells with hybrid cells in the presence of a cytokine.  
     
     
         14 . The population of  claim 13 , wherein the cytokine is IL-2.  
     
     
         15 . A composition comprising the population of antigen-specific immune effector cells of  claim 1  and a pharmaceutically acceptable carrier.  
     
     
         16 . The population according to  claim 1 , wherein the immune effector cells are produced by contacting immune effector cells with hybrid cells in the presence of a cytokine.  
     
     
         17 . The population of  claim 16 , wherein the cytokine is IL-2.  
     
     
         18 . A composition comprising the population of antigen-specific immune effector cells of  claim 6  and a pharmaceutically acceptable carrier.