Vaccine immunotherapy

Abstract

The present invention provides compositions and methods of immunotherapy to treat cancer or other antigen-producing diseases or lesions. According to one embodiment of the invention, a composition is provided for eliciting an immune response to at least one antigen in a patient having an antigen-producing disease or lesion, the composition comprising an effective amount of a cytokine mixture, preferably comprising IL-1, IL-2, IL-6, IL-8, IFN-γ (gamma) and TNF-α (alpha). The cytokine mixture acts as an adjuvant with the antigen associated with the antigen-producing disease or lesion to enhance the immune response of the patient to the antigen. Methods are therefore also provided for eliciting an immune response to at least one antigen in a patient having an antigen-producing disease or lesion utilizing the cytokine mixture of the invention. The compositions and methods are useful in the treatment of antigen-producing diseases such as cancer, infectious diseases or persistent lesions.

1 . A composition for eliciting an immune response to at least one antigen in a patient having an antigen-producing disease or lesion comprising an effective amount of a cytokine mixture including the cytokines IL-1, IL-2, IL-6, IL-8, IFN-γ, and TNF-α, wherein the cytokines act as an adjuvant with the antigen and stimulate an immune response to the antigen in the patient.  
   
   
       2 . The composition of  claim 1 , wherein the cytokines are naturally made or recombinant cytokines, or a mixture of naturally made and recombinant cytokines.  
   
   
       3 . The composition of  claim 1 , wherein the cytokines are pegylated or a mixture of naturally made, recombinant or pegylated cytokines.  
   
   
       4 . The composition of  claim 1 , wherein the cytokine mixture further comprises IL-12, GM-CSF and G-CSF, wherein the IL-12, GM-CSF and G-CSF are naturally made or recombinant cytokines, or a mixture of naturally made and recombinant cytokines.  
   
   
       5 . The composition of  claim 1 , wherein the cytokine mixture further comprises IL-12, GM-CSF and G-CSF, wherein the IL-12, GM-CSF and G-CSF are pegylated cytokines, or a mixture of naturally made, recombinant or pegylated cytokines.  
   
   
       6 . The composition of  claim 1 , wherein the antigen-producing disease is cancer.  
   
   
       7 . The composition of  claim 6 , wherein the cancer is selected from the group consisting of squamous cell carcinoma of the head and neck, prostate cancer, melanoma, breast cancer, lymphoma, cervical cancer and hepatoma.  
   
   
       8 . The composition of  claim 1 , wherein the antigen-producing lesion is a non-cancerous persistent lesion.  
   
   
       9 . The composition of  claim 1 , wherein the antigen is an endogenous antigen, an exogenous antigen or a combination thereof.  
   
   
       10 . The composition of  claim 1 , wherein the antigen is an endogenous antigen.  
   
   
       11 . The composition of  claim 1 , wherein the antigen is an exogenous antigen.  
   
   
       12 . The composition of  claim 1 , further comprising an effective amount of at least one exogenous antigen, wherein the combination of the cytokines and exogenous antigen stimulates an immune response to the exogenous antigen.  
   
   
       13 . The composition of  claim 1 , wherein the antigen is a tumor antigen.  
   
   
       14 . The composition of  claim 13 , wherein the tumor antigen is a protein or a peptide.  
   
   
       15 . The composition of  claim 12 , wherein the antigen is a tumor antigen.  
   
   
       16 . The composition of  claim 15 , wherein the tumor antigen is a protein or a peptide.  
   
   
       17 . A method of eliciting an immune response to at least one antigen in a patient having an antigen-producing disease or lesion comprising administering an effective amount of a cytokine mixture comprising IL-1, IL-2, IL-6, IL-8, IFN-γ, and TNF-α, wherein the cytokines act as an adjuvant with the antigen and stimulate an immune response to the antigen in the patient.  
   
   
       18 . The method of  claim 17 , wherein the cytokines are naturally made or recombinant cytokines, or a mixture of naturally made and recombinant cytokines.  
   
   
       19 . The method of  claim 17 , wherein the cytokines are pegylated or a mixture of naturally made, recombinant or pegylated cytokines.  
   
   
       20 . The method of  claim 17 , wherein the cytokine mixture further comprises IL-12, GM-CSF and G-CSF, wherein the IL-12, GM-CSF and G-CSF are naturally made or recombinant cytokines, or a mixture of naturally made and recombinant cytokines.  
   
   
       21 . The method of  claim 17 , wherein the cytokine mixture further comprises IL-12, GM-CSF and G-CSF, wherein the IL-12, GM-CSF and G-CSF are pegylated cytokines, or a mixture of naturally made, recombinant or pegylated cytokines.  
   
   
       22 . The method of  claim 17 , wherein the antigen-producing disease is cancer.  
   
   
       23 . The method of  claim 22 , wherein the cancer is selected from the group consisting of squamous cell carcinoma of the head and neck, prostate cancer, melanoma, breast cancer, lymphoma, cervical cancer and hepatoma.  
   
   
       24 . The method of  claim 17 , wherein the antigen-producing lesion is a non-cancerous persistent lesion.  
   
   
       25 . The method of  claim 17 , wherein the antigen is an endogenous antigen, an exogenous antigen or a combination thereof.  
   
   
       26 . The method of  claim 17 , wherein the antigen is an endogenous antigen.  
   
   
       27 . The method of  claim 17 , wherein the antigen is an exogenous antigen.  
   
   
       28 . The method of  claim 17 , comprising a further step of administering to the patient an effective amount of at least one exogenous antigen, wherein the combination of the cytokine mixture and exogenous antigen stimulates an immune response to the exogenous antigen.  
   
   
       29 . The method of  claim 17 , wherein the antigen is a tumor antigen.  
   
   
       30 . The method of  claim 29 , wherein the tumor antigen is a protein or a peptide.  
   
   
       31 . The method of  claim 28 , wherein the antigen is a tumor antigen.  
   
   
       32 . The method of  claim 31 , wherein the tumor antigen is a protein or a peptide.  
   
   
       33 . The method of  claim 17 , wherein said administering step is defined as administering IL-2 at a concentration ranging from 600 to 60,000 pcg/ml.  
   
   
       34 . The method of  claim 17 , wherein said administering step is defined as administering IL-2 at a concentration ranging from 3,000 to 12,000 pcg/ml.  
   
   
       35 . The method of  claim 17 , wherein said administering step is defined as administering IL-2 at a concentration ranging from 4,000 to 8,000 pcg/ml.  
   
   
       36 . The method of  claim 17 , wherein the cytokine mixture is administered by perilymphatic injection.  
   
   
       37 . The method of  claim 17 , wherein the cytokine mixture is administered by bilateral perilymphatic injection.  
   
   
       38 . The method of  claim 26 , wherein said administering step is defined as administering the cytokine mixture for at least 1 to 20 days.  
   
   
       39 . The method of  claim 28 , wherein said administering step is further defined as administering the cytokine mixture and the exogenous antigen on an approximately monthly basis.  
   
   
       40 . The method of  claim 17 , wherein said administering step is defined as administering the cytokine mixture prior to surgery, radiotherapy or chemotherapy, or combinations of surgery, radiotherapy or chemotherapy.  
   
   
       41 . The method of  claim 17 , wherein said administering step is defined as administering the cytokine mixture following the recurrence of tumors.  
   
   
       42 . The method of  claim 17 , further including the step of administering an effective amount of cyclophosphamide (CY).  
   
   
       43 . The method of  claim 17 , further including the step of administering an effective amount of a nonsteroidal anti-inflammatory drug (NSAID) selected from the group consisting of indomethacin (INDO), Ibuprofen, celecoxib (Celebrex®), rofecoxib (Vioxx®), Coxil inhibitors, and combinations thereof.  
   
   
       44 . A method of immunotherapy to treat cancer comprising the step of administering an effective amount of a cytokine mixture comprising IL-1, IL-2, IL-6, IL-8, IFN-γ, and TNF-α, wherein the cytokine mixture acts as an adjuvant and stimulates an immune response in the patient.  
   
   
       45 . The method of  claim 44 , further comprising the step of administering an effective amount of at least one exogenous cancer antigen to the patient.  
   
   
       46 . The method of  claim 44  or  45 , wherein the cancer is selected from the group consisting of squamous cell carcinoma of the head and neck, prostate cancer, melanoma, breast cancer, lymphoma, cervical cancer and hepatoma.  
   
   
       47 . The method of  claim 44  or  45 , wherein the cancer is squamous cell carcinoma of the head and neck.