Autologous T-cell vaccines materials and methods

Abstract

The present invention relates to improved autologous T cell vaccines and methods for their production. The invention is also directed to methods for treating T cell associated diseases such as multiple sclerosis and rheumatoid arthritis using autologous T cell vaccines.

1 . A method for treating multiple sclerosis comprising administering to a patient in need thereof an autologous T cell vaccine, wherein the vaccine comprises attenuated T cells that are reactive against one or more epitopes, wherein amino acids 83-99 and 151-170 of myelin basic protein comprise the epitopes.  
     
     
         2 . The method of  claim 1  wherein only amino acids 83-99 and 151-170 of myelin basic protein comprise the epitopes.  
     
     
         3 . The method of  claim 1  wherein the vaccine consisting essentially of T cells that are reactive against myelin basic protein at amino acids 83-99 or 151-170.  
     
     
         4 . The method of  claim 1  wherein the vaccine further comprises attenuated T cells that are reactive against proteolipid lipoprotein, myelin oligodendrocyte glycoprotein, or a combination thereof.  
     
     
         5 . The method of  claim 1  wherein the vaccine is administered at a dosage of 80×10 6  to 160×10 6  T cells.  
     
     
         6 . The method of  claim 5  wherein the vaccine is administered at two month intervals.  
     
     
         7 . The method of  claim 6  wherein the vaccine is administered three times.  
     
     
         8 . A method for treating multiple sclerosis comprising administering to a patient in need thereof an autologous T cell vaccine, wherein the vaccine is made by a process comprising: 
 (a) incubating a plurality of mononuclear cells comprising T cells in the presence of an antigen, wherein the cells are obtained from the patient to be treated with the vaccine;    (b) stimulating the cells of (a) with antigen presenting cells and the antigen;    (c) alternatively the cells of (b) one or more times by a process comprising: 
 (i) stimulating the cells with the antigen; and  
 (ii) stimulating the cells of (i) with a mitogen in the presence of IL-2; and  
   (d) attenuating the cells,    wherein the antigen comprises fragments of myelin basic protein consisting essentially of amino acids 83-99 and 151-170.    
     
     
         9 . The method of  claim 8  wherein the antigen consists essentially of the fragments of myelin basic protein.  
     
     
         10 . The method of  claim 8  wherein the antigen further comprise proteolipid lipoprotein, myelin oligodendrocyte glycoprotein, or a combination thereof.  
     
     
         11 . The method of  claim 10  wherein the vaccine is administered at a dosage of 80×10 6  to 160×10 6  T cells.  
     
     
         12 . The method of  claim 11  wherein the vaccine is administered at two month intervals.  
     
     
         13 . The method of  claim 12  wherein the vaccine is administered three times.