Methods for treating refractory infections in neutropenic individuals

Abstract

The invention is based, in part, on the discovery of a novel cell-based immunotherapy that can recapitulate neutrophil functions in neutropenic individuals afflicted with a microbial infection. The therapeutic compositions and methods of the invention are broadly applicable to treat any infection in a neutropenic individual, including infections caused by bacteria, fungi, protozoa, and viruses. The invention compositions of activated, irradiated HL-60 cells represent a practical, rapid cell-based immunotherapy for refractory infections.

1 . A composition comprising an activated and irradiated HL-60 cell line.  
   
   
       2 . The composition of  claim 1 , wherein said activation lasted for at least a three day period.  
   
   
       3 . The composition of  claim 1 , wherein said activation comprised the presence of retinoic acid (RA) and dimethylsulfoxide (DMSO).  
   
   
       4 . The composition of  claim 1 , wherein said irradiation was at least 1500 rads.  
   
   
       5 . The composition of  claim 1 , wherein said HL-60 cells have no replicative capacity.  
   
   
       6 . The composition of  claim 1 , flow cytometric parameters distinguish said activated HL-60 cells from unactivated HL-60 cells.  
   
   
       7 . The composition of  claim 6 , wherein said flow cytometric parameters are selected from the group comprising cell viability, cell size, and change in cell size during activation.  
   
   
       8 . The composition of  claim 7 , wherein said HL-60 cells have antimicrobial activity.  
   
   
       9 . The composition of  claim 8 , wherein said antimicrobial activity comprises anti-candidal activity.  
   
   
       10 . The composition of  claim 9 , wherein said flow cytometric changes are inversely correlated with anti-candidal capacity.  
   
   
       11 . A method of reducing or inhibiting growth or survival of a microorganism in an environment capable of sustaining the growth or survival of the microorganism, comprising administering an effective amount of an activated and irradiated human myeloid cell line to said environment, thereby reducing or inhibiting the growth or survival of the microorganism.  
   
   
       12 . The method of  claim 10 , wherein said microorganism is a pathogenic fungus.  
   
   
       13 . The method of  11 , wherein said microorganism is  Candida.    
   
   
       14 . The method of  claim 12 , wherein said  Candida  is  Candida albicans    
   
   
       15 . The method of  claim 1   1 , wherein said human myeloid cell line is an HL-60 cell line.  
   
   
       16 . The method of  claim 11 , wherein said cell line was activated in the presence of retinoic acid (RA) and dimethylsulfoxide (DMSO).  
   
   
       17 . The method of  claim 1   1 , wherein said human myeloid cell line was irradiated by at least 1500 rads.  
   
   
       18 . The method of  claim 11 , wherein said human myeloid cell line has no replicative capacity.  
   
   
       19 . A method for treating hematogenously disseminated fungal infection in an individual, said method comprising transfusion of an effective amount of an activated and irradiated HL-60 cell line to an individual afflicted with a hematogenously disseminated fungal infection.  
   
   
       20 . The method of  claim 19 , wherein the fungal infection is candidiasis.  
   
   
       21 . The method of  claim 20 , wherein the candidiasis is caused by  Candida albicans.    
   
   
       22 . The method of  claim 19 , wherein said HL-60 cell line was activated for a duration of at least a three days.  
   
   
       23 . The method of  claim 22 , wherein said HL-60 cell line was activated in the presence of retinoic acid (RA) and dimethylsulfoxide (DMSO).  
   
   
       24 . The method of  claim 19 , wherein said HL-60 cell line was irradiated with at least 1500 rads.  
   
   
       25 . The method of  claim 24 , wherein said HL-60 cells have no replicative capacity.  
   
   
       26 . A method for treating neutropenia in an individual, said method comprising transfusion of an effective amount of an irradiated and activated activated and irradiated HL-60 cell line to an individual afflicted with neutropenia.  
   
   
       27 . The method of  claim 26 , wherein said neutropenia is transient.  
   
   
       28 . The method of  claim 27 , wherein said transient neutropenia is associated with a microbial infection.  
   
   
       29 . A method for treating hematogenously disseminated fungal infection in an individual, said method comprising transfusion of an effective amount of the composition of  claim 10 .  
   
   
       30 . A method for treating neutropenia in an individual, said method comprising transfusion of an effective amount of  claim 7.