Vaccination with immuno-isolated cells producing an immunomodulator

Abstract

The present invention relates to immuno-protected encapsulated cells producing an immunomodulator, for example GM-CSF (granulocyte-macrophage colony stimulating factor). The cells of the invention are particularly well adapted for providing an active adjuvant or immunomodulator, for example in the context of immunisation in humans and animals. These cells can be used for vaccination where they provide the immunomodulator in an active form, in a continuous, non-immunogenic manner in the immediate vicinity of the vaccine antigen(s). The invention also relates to a vaccine composition comprising immuno-protected encapsulated cells producing an immunomodulator and an antigenic component. The invention also relates to a kit comprising a cell as described and an antigenic component. The strategy of the invention is perfectly suited for both cancer immunotherapy and vaccination against infectious agents.

1 . A cell producing at least one immunomodulatory agent, said cell being immuno-isolated.  
   
   
       2 . The cell according to  claim 1 , wherein said immunomodulatory agent is an immunostimulatory agent.  
   
   
       3 . The cell according to  claim 1 , wherein said immunomodulatory agent is a cytokine.  
   
   
       4 . The cell according to  claim 3 , wherein said cytokine is GM-CSF.  
   
   
       5 . The cell according to  claim 3 , wherein said cytokine is FL.  
   
   
       6 . The cell according to  claim 1 , further producing another immunomodulatory agent.  
   
   
       7 . The cell according to  claim 1 , further producing an antigenic agent.  
   
   
       8 . The cell according to  claim 1 , wherein said produced immunomodulatory agent is secreted.  
   
   
       9 . The cell according to  claim 1 , wherein said immuno-isolation is achieved by a barrier device.  
   
   
       10 . The cell according to  claim 1 , wherein said immuno-isolation is achieved by microencapsulation.  
   
   
       11 . The cell according to  claim 1 , wherein said immuno-isolation is achieved by macroencapsulation.  
   
   
       12 . The cell according to  claim 9 , wherein said barrier device is selectively permeable.  
   
   
       13 . The cell according to  claim 12 , wherein said barrier device is selectively permeable to molecules with molecular weight smaller than 280 kDa.  
   
   
       14 . The cell according to  claim 1 , wherein said cell is genetically modified to express the immunomodulatory agent.  
   
   
       15 . The cell according to  claim 14 , wherein the genetic modification is achieved by transfection by a plasmid or infection by a virus.  
   
   
       16 . The cell according to  claim 1 , wherein said cell is a human established cell line, for instance a fibroblast or an epithelial cell line.  
   
   
       17 . The cell according to  claim 1 , wherein said cell is immortal or immortalised.  
   
   
       18 . The cell according  claim 1 , wherein said cell is non tumoral.  
   
   
       19 . The cell according to  claim 1 , wherein said cell is of mammal origin.  
   
   
       20 . The cell according to  claim 1 , wherein said cell is human.  
   
   
       21 . The cell according to  claim 1 , wherein said cell is irradiated.  
   
   
       22 . The cell according to  claim 1 , wherein said cell secretes between 80 and 960×10 −15  g/24 hr of immunomodulatory agent.  
   
   
       23 . The cell according to  claim 1 , wherein said cell secretes more than 10×10 −15  g/24 hr, preferably more than 100×10 −15  g/24 hr of immunomodulatory agent.  
   
   
       24 . A pharmaceutical composition comprising a cell according to  claim 1  and a physiologically acceptable carrier.  
   
   
       25 . A vaccine composition comprising a cell according to  claim 1  and an antigenic component.  
   
   
       26 . The vaccine composition according to  claim 25 , wherein said antigenic component is a tumour cell.  
   
   
       27 . The vaccine composition according to  claim 26 , wherein said tumour cell is irradiated.  
   
   
       28 . The vaccine composition according to  claim 25 , wherein said antigenic component is from an infectious agent.  
   
   
       29 . The vaccine composition according to  claim 28 , wherein said infectious agent is a virus.  
   
   
       30 . The vaccine composition according to  claim 29 , wherein said virus is Hepatitis C or HIV.  
   
   
       31 . A kit comprising a cell according to  claim 1  and an antigenic component.  
   
   
       32 . The kit according to  claim 31 , wherein the antigenic component comprises a cell producing or releasing one or several antigens.  
   
   
       33 . The kit according to  claim 32 , wherein said cell producing or releasing one or several antigens is a tumour cell.  
   
   
       34 . The kit according to  claim 33 , wherein said tumour cell is irradiated.  
   
   
       35 . The kit according to  claim 31 , wherein the antigenic component is from an infectious agent.  
   
   
       36 . The kit according to  claim 35 , wherein said infectious agent is a virus.  
   
   
       37 . The kit according to  claim 31  which is biocompatible.  
   
   
       38 . The kit according to  claim 31  which can be inserted into human body.  
   
   
       39 . A capsule containing at least one cell producing an immunomodulator.  
   
   
       40 . The capsule according to  claim 39 , wherein said immunomodulator is GM-CSF.  
   
   
       41 . The capsule according to  claim 39  also containing a polymer matrix.  
   
   
       42 . The capsule according to  claim 39  which is designed to be removable after insertion.  
   
   
       43 . The capsule according to  claim 39 , wherein said capsule is irradiated.  
   
   
       44 . The cell according to  claim 1  for use in therapy or vaccination.  
   
   
       45 . A use of a cell according to  claim 1  for the manufacture of an adjuvant for enhancing immune response.  
   
   
       46 . A use of a cell according to  claim 1  for the manufacture of a medicament for the treatment or prevention of cancer.  
   
   
       47 . A use of a kit according to  claim 31  for the manufacture of a vaccine.  
   
   
       48 . The use according to  claim 47 , wherein said vaccine is to be implanted and subsequently removed.  
   
   
       49 . The use according to  claim 48 , wherein removal is accomplished between 2 to 7 days after implantation, preferably between 5 to 7 days.  
   
   
       50 . The use according to  claim 45 , wherein said cells are irradiated.