Synergistic composition and methods for treating neoplastic or cancerous growths and for restoring or boosting hematopoiesis

Abstract

The present invention provides a synergistic composition and methods for treating neoplastic or cancerous growths as well as for treating such patients in order to restore or boost hematopoiesis. The present invention comprises administration of the combination of a cytotoxic T-lymphocyte inducing composition and at least one agent which is capable of neutralizing or down regulating the activity of tumor secreted immunosuppressive factors, separately or in combination.

1 - 37 . (canceled)  
   
   
       38 . A method of treating infection by a virus comprising administering to a patient in need thereof: 
 (a) an admixture comprising a viral antigen expressed by cells infected by said virus and a microfluidized antigen formulation comprising:    (i) a stabilizing detergent,    (ii) a micelle-forming agent, and    (iii) a biodegradable and biocompatible oil,    said antigen formulation being formulated as a stable oil-in-water emulsion; wherein said admixture is administered to said patient in an amount sufficient to induce a cytotoxic T-lymphocyte response in said patient which is specific for the viral antigen contained in said admixture, and    (b) a therapeutically effective amount of at least one agent which is capable of neutralizing, blocking, antagonizing, or down regulating the activity or preventing activation of transforming growth factor β (TGFβ) specifically, which agent is selected from the group consisting of an anti-TGFβ antibody, a TGFβR-fusion protein, a TGFβ analog, a TGFβ binding protein, and a TGFβR blocking antibody;    wherein the antigen-containing admixture and the at least one agent which is capable of neutralizing, blocking, antagonizing, or down regulating the activity or preventing activation of TGFβ are administered sequentially or concurrently, and in any order.    
   
   
       39 . The method of  claim 38 , wherein the antigen-containing admixture and the at least one agent which is capable of neutralizing, blocking, antagonizing, or down regulating the activity or preventing activation of TGFβ are administered sequentially.  
   
   
       40 . The method of  claim 38 , wherein the antigen-containing admixture is administered intradermally, intramuscularly or subcutaneously and the at least one agent which is capable of neutralizing, blocking, antagonizing, or down regulating the activity or preventing activation of TGFβ is administered intravenously.  
   
   
       41 . The method of  claim 38 , wherein the at least one agent which is capable of neutralizing, blocking, antagonizing, or down regulating the activity or preventing activation of TGFβ is a thrombospondin peptide or a TGFβR Fc-fusion protein.  
   
   
       42 . The method of  claim 38 , wherein the virus is selected from the group consisting of Epstein Barr virus (EBV), human papillomavirus (HPV), human immunodeficiency virus (HIV), influenza virus, Hepatitis A virus, Hepatitis B virus, Hepatitis C virus, Herpes virus (HSV), cytomegalovirus, and respiratory syncytial virus.  
   
   
       43 . The method of  claim 42 , wherein the admixture comprises a viral antigen selected from the group consisting of EBNA gene products of EBV; E6 protein of HPV; E7 protein of HPV, gp160 protein of HIV, gag protein of HIV, pol protein of HIV, nef protein of HIV, Tat protein of HIV, Rev protein of HIV, surface antigenic proteins of Hepatitis A virus, Pre-S1 protein of Hepatitis B virus, Pre-S2 protein of Hepatitis B virus, HBc Ag protein of Hepatitis B virus, HBe Ag protein of Hepatitis B virus, surface antigenic proteins of Hepatitis C virus, HA protein of influenza virus, NP protein of influenza virus, NA protein of influenza virus, gB protein of HSV, gD protein of HSV, gH protein of HSV, early protein product of HSV, gB protein of cytomegalovirus, gH protein of cytomegalovirus, IE protein gp72 of cytomegalovirus, F protein of respiratory syncytial virus, G protein of respiratory syncytial virus, and N protein of respiratory syncytial virus.  
   
   
       44 . The method of  claim 38 , wherein the detergent is provided in an amount ranging from approximately 0.05 to 0.5%.  
   
   
       45 . The method of  claim 38 , wherein the amount of detergent is about 0.2%.  
   
   
       46 . The method of  claim 38 , wherein the detergent is selected from the group consisting of sorbitan-mono-9-octadecenoate-poly(oxy)-1,2-ethanediyl, polyoxyethylene-sorbitan monolaurate, polyoxyethylenesorbitan monopalmitate, polyoxyethylenesorbitan monostearate, N-dodecyl-N,N-dimethyl-3-ammonio-1-propanesulfonate, alkyl (C 9 -C 13 ) sodium sulfates, and sorbitan trioleate.  
   
   
       47 . The method of  claim 38 , wherein the micelle-forming agent has a hydrophile-lipophile balance of between 0 and 2.  
   
   
       48 . The method of  claim 38 , wherein the amount of the micelle-forming agent ranges from 0.5 to 10%.  
   
   
       49 . The method of  claim 48 , wherein the amount of the micelle-forming agent ranges from 1.25 to 5%.  
   
   
       50 . The method of  claim 38 , wherein the amount of oil ranges from 1 to 10%.  
   
   
       51 . The method of  claim 50 , wherein the amount of oil ranges from 2.5 to 5%.  
   
   
       52 . The method of  claim 38 , wherein the oil exhibits a melting temperature of less than 65° C.  
   
   
       53 . The method of  claim 38 , wherein the oil is selected from the group consisting of squalane, eicosane, tetratetracontane, pristane, and vegetable oils.  
   
   
       54 . The method of  claim 38 , wherein the antigen-containing admixture comprises sorbitan-mono-9-octadecenoate-poly(oxy)-1,2-ethanediyl, a block copolymer having the structure:  
     
       
         
         
             
             
         
       
     
     wherein a and b are such that the average molecular weight of the polyoxypropylene blocks in the molecule is 4000 and approximately 10% of the molecular weight of the copolymer is composed of the polyoxyethylene blocks, and squalane.  
   
   
       55 . The method of  claim 38 , wherein the antigen-containing admixture contains no more than 20 micrograms of an immunostimulating muramyl dipeptide.  
   
   
       56 . The method of  claim 38 , wherein the antigen-containing admixture lacks an immunostimulating muramyl dipeptide.