Induction of cytotoxic T-lymphocyte responses

Abstract

Methods and compositions useful for inducing a cytotoxic T lymphocyte response (CTL) in a human or domesticated or agriculturally important animal. The method includes the steps of providing the antigen to which the CTL response is desired and providing a microfluidized antigen formulation which comprises, consists, or consists essentially of two or more of a stabilizing detergent, a micelle-forming agent, and an oil. This antigen formulation is preferably lacking in an immunostimulating peptide component, or has sufficiently low levels of such a component that the desired CTL response is not diminished. This formulation is provided as a stable oil-in-water emulsion.

1 - 20 . (canceled)  
     
     
         21 . A method of treating a patient suffering from cancer, comprising administering a composition comprising a neu oncogene product antigen mixed with a microfluidized antigen formulation comprising: 
 (a) a stabilizing detergent,    (b) a micelle-forming agent, and    (c) a biodegradable and biocompatible oil,    said antigen formulation being substantially free of an immunostimulating peptide component, and being formulated as a stable oil-in-water emulsion; wherein said composition is administered to said patient in an amount sufficient to induce a cytotoxic T-lymphocyte response against cancer cells that express neu oncogene product in said patient.    
     
     
         22 - 38 . (canceled)  
     
     
         39 . A method of treating a patient suffering from cancer, comprising administering a composition comprising a neu oncogene product antigen mixed with a microfluidized antigen formulation consisting essentially of two of: 
 (a) a stabilizing detergent,    (b) a micelle-forming agent, and    (c) a biodegradable and biocompatible oil,    said antigen formulation being formulated as a stable oil-in-water emulsion; wherein said composition is administered to said patient in an amount sufficient to induce a cytotoxic T-lymphocyte response against cancer cells that express neu oncogene product in said patient.    
     
     
         40 - 67 . (canceled)  
     
     
         68 . The method of  claim 21 , wherein the detergent is selected from the group consisting of Tween 80 (polyoxyethylene sorbitan monooleate), Tween 20 (polyoxyethylene sorbitan monolaurate), Tween 40 (polyoxyethylene sorbitan monopalmitate), Tween 60 (polyoxyethylene sorbitan monostearate), Zwittergent 3-12, Teepol HB7 and Span 85.  
     
     
         69 - 75 . (canceled)  
     
     
         76 . The method of claim  7   21 , wherein the oil is selected from the group consisting of squalane, squalene, eicosane, tetratetracontane, pristane, glycerol, and vegetable oils.  
     
     
         77 - 78 . (canceled)  
     
     
         79 . The method of  claim 21 , wherein the admixture comprises less than 20 micrograms of muramyl dipeptide.  
     
     
         80 . The method of  claim 21 , wherein the admixture does not contain any muramyl dipeptide.  
     
     
         81 . The method of  claim 21 , wherein the detergent is Tween 80, the micelle-forming agent is poloxamer 401, and the oil is squalane.  
     
     
         82 - 85 . (canceled)  
     
     
         86 . The method of  claim 21 , wherein the patient is a human.  
     
     
         87 . The method of  claim 21 , wherein the neu oncogene product antigen is an antigenic portion of neu oncogene product.  
     
     
         88 . The method of  claim 39 , wherein the detergent is selected from the group consisting of Tween 80, Tween 20, Tween 40, Tween 60, Zwittergent 3-12, Teepol HB7 and Span 85.  
     
     
         89 . The method of  claim 39 , wherein the oil is selected from the group consisting of squalane, squalene, eicosane, tetratetracontane, pristane, glycerol, and vegetable oils.  
     
     
         90 . The method of  claim 39 , wherein the detergent is Tween 80 and the oil is squalane.  
     
     
         91 . The method of  claim 39 , wherein the patient is a human.  
     
     
         92 . The method of  claim 39 , wherein the neu oncogene product antigen is an antigenic portion of neu oncogene product.  
     
     
         93 . A method for inducing a cytotoxic T-lymphocyte response against cancer cells that express neu oncogene product in a human or domesticated or agricultural animal, comprising the steps of: 
 administering a mixture of a neu oncogene product antigen mixed with a microfluidized antigen formulation comprising:    (a) a detergent selected from the group consisting of Tween 80, Tween 20, Tween 40, Tween 60, Zwittergent 3-12, Teepol HB7 and Span 85, and    (b) an oil selected from the group consisting of oil squalane, squalene, eicosane, tetratetracontane, pristane, glycerol, and vegetable oils,    said antigen formulation being formulated as a stable oil-in-water emulsion; wherein said mixture is administered to said human or animal in an amount sufficient to induce a cytotoxic T-lymphocyte response against cancer cells that express neu oncogene product in said human or animal.    
     
     
         94 . The method of  claim 93 , wherein a cytotoxic T-lymphocyte response is induced in a human.  
     
     
         95 . The method of  claim 93 , wherein the neu oncogene product antigen is an antigenic portion of neu oncogene product.  
     
     
         96 . The method of  claim 93 , wherein the microfluidized antigen formulation consists essentially of said detergent and said oil.  
     
     
         97 . The method of  claim 96 , wherein the detergent is Tween 80.  
     
     
         98 . The method of  claim 97 , wherein the oil is squalane.