Autologous T-cell vaccines materials and methods
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.