Immunotherapy for reversing immune suppression

Abstract

A method for overcoming immune suppression includes the steps of inducing production of naïve T cells and restoring T cell immunity. A method of vaccine immunotherapy includes the steps of inducing production of naïve T cells and exposing the naïve T cells to endogenous or exogenous antigens at an appropriate site. Additionally, a method for unblocking immunization at a regional lymph node includes the steps of promoting differentiation and maturation of immature dendritic cells at a regional lymph node and allowing presentation of processed peptides by resulting mature dendritic cells, thus, for example, exposing tumor peptides to T cells to gain immunization of the T cells. Further, a method of treating cancer and other persistent lesions includes the steps of administering an effective amount of a natural cytokine mixture as an adjuvant to endogenous or exogenous administered antigen to the cancer or other persistent lesions; preferably the natural cytokine mixture is administered in combination with thymosin α 1 .

1 . A method for unblocking immunization at a regional lymph node by: promoting maturation and activation of dendritic cells in a regional lymph node; and allowing presentation by resulting mature dendritic cells of antigen to T cells to gain immunization of the T cells to the antigen. 
     
     
         2 . A method according to  claim 1 , wherein said promoting step is further defined as administering a natural cytokine mixture (NCM)+thymosin α 1  perilymphatically into lymphatics that drain into lymph nodes regional to a lesion to be treated. 
     
     
         3 . A method according to  claim 1 , wherein the lesion is a cancerous or non-cancerous persistent lesion. 
     
     
         4 . A method according to  claim 3 , wherein the non-cancerous persistent lesion is infectious. 
     
     
         5 . (canceled) 
     
     
         6 . A method according to  claim 1 , wherein the antigen is an exogenous antigen. 
     
     
         7 . (canceled) 
     
     
         8 . A method of inducing immunization to cancer or persistent lesions by:
 administering an effective amount of an exogenous antigen and an adjuvant consisting of a NCM+thymosin α 1 .   
     
     
         9 . A method according to  claim 8 , wherein said administering step is further defined as administering an NCM including IL-1, IL-2, IL-6, IL-8, IL-10, IL-12, δIFNIFN-γ, TNF-α, FGM-CSFG-CSF, GM-CSF+thymosin α 1 . 
     
     
         10 . A method according to  claim 8 , wherein said administering step is further defined as injecting the NCM+thymosin α 1  perilymphatically, intranodally, intralymphatically, intrasplenically, subcutaneously, intramuscularly, or intracutaneously. 
     
     
         11 - 16 . (canceled) 
     
     
         17 . A method of treating a cancer or other persistent lesion in a severely an immune suppressed patient by administering to the patient an effective amount of a NCM which acts as an adjuvant to endogenous or exogenously administered antigen from the cancer or persistent lesion to stimulate an immune response in the patient. 
     
     
         18 . A method according to  claim 17 , wherein said administering step is further defined as injecting an NCM including IL-1, IL-2, IL-6, IL-8, TNFα, and IFN+thymosin α 1 . 
     
     
         19 . A method according to  claim 18 , wherein said administering step is further defined as injecting an NCM including IL-1, IL-2, IL-6, IL-8, TNFα, and IFN-γ, +thymosin α 1 . 
     
     
         20 . A method according to  claim 17 , further including the steps of blocking endogenous suppression of T cells directly or indirectly by the endogenous lesion being treated by codelivering cyclophosphamide and a nonsteroidal anti-inflammatory drug (NSAID). 
     
     
         21 . A method according to  claim 17 , wherein said blocking and inducing steps are further defined as codelivering cyclophosphamide and a nonsteroidal anti-inflammatory drug (NSAID). 
     
     
         22 . A method according to  claim 21 , wherein the NSAIDs are selected from the group including indomethacin, Ibuprofen, rofecoxib, celecoxib and other related treated compounds. 
     
     
         23 . A method of vaccine immunotherapy including the steps of:
 inducing production of naïve T cells; and   exposing the naïve T cells to endogenous or exogenous antigens.   
     
     
         24 . A method according to  claim 23 , wherein said exposing step is further defined as exposing the naïve T cells to endogenously processed peptide preparation resident in regional nodes of a patient who possesses a lesion. 
     
     
         25 . A method according to  claim 24 , wherein the lesion is cancerous or infectious. 
     
     
         26 . A method according to  claim 23 , wherein said exposing step is further defined as administering an exogenously produced antigen. 
     
     
         27 . A method according to  claim 23 , wherein said antigen is otherwise nonimmunogenic peptide. 
     
     
         28 . A method according to  claim 23 , wherein said exposing step is further defined as immunizing the naïve T cells with matured peptide presenting dendritic cells at a lymph node distal from a lesion to be treated. 
     
     
         29 . A method of treating lymphocytopenia by administering an effective amount of NCM. 
     
     
         30 . A method of inducing immunity by:
 inducing in vivo maturation of dendritic cells resulting in effective antigen presentation to naïve uncommitted T cells, leading to clonal expansion of t and B cells, thereby creating immunity in a patient.   
     
     
         31 . A method according to  claim 29 , including the further step of infiltrating into tumors by hematogenous spread leading to tumor destruction. 
     
     
         32 . A method of inducing immunity by:
 generating a microenvironment in a regional lymp node allowing effective antigen processing and presentation; and   decreasing cells of the lineage of dendritic cells in the lymph node sinuses that accumulate in a cancer patient so that antigen becomes immunogenic for T cells.