Autologous T-cell vaccines materials and methods
View Patent ↗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 are rheumatoid arthritis using autologous T cell vaccines.
1. An autologous T cell vaccine for the treatment of multiple sclerosis made by a process comprising:
(a) obtaining a plurality of mononuclear cells comprising T cells from a patient to be treated with the vaccine;
(b) incubating the T cells in the presence of a human multiple sclerosis associated antigen;
(c) stimulating the T cells obtained in step b) with antigen presenting cells APC(s) and the multiple sclerosis associated antigen;
(d) stimulating the T cells of step c) with the multiple sclerosis associated antigen;
(e) stimulating the T cells of step d) with a mitogen in the presence of IL-2;
(f) repeating steps d) and e) one or more times; and
(g) irradiating the T cells,
wherein the multiple sclerosis antigen consists of amino acids 83-99 of myelin basic protein and amino acids 151-170 of myelin basic protein.
2. The T cell vaccine according to claim 1 wherein the plurality of mononuclear cells is obtained from the peripheral blood (PBMC) from said patient.
3. The T cell vaccine according to claim 1 wherein the plurality of mononuclear cells is obtained from the cerebrospinal fluid (CSFMC) of the patient.
4. The vaccine of claim 1 wherein IL-2 is added to the T cell in each of steps c), d), e) and f).
5. The vaccine of claim 1 wherein said APCs are irradiated PBMCs or CSFMCs obtained from the patient to be treated.
6. The vaccine of claim 1 wherein the mitogen is selected from the group consisting of phytohemagglutinin, conconavalin A, pokeweed mitogen, and monoclonal antibodies to CD3.
7. A method for preparing an autologous T cell vaccine for the treatment of multiple sclerosis made by a process comprising:
(a) obtaining a plurality of mononuclear cells comprising T cells from a patient to be treated with the vaccine;
(b) incubating the T cells in the presence of a human multiple sclerosis associated antigen;
(c) stimulating the T cells obtained in step b) with antigen presenting cells APC(s) and the multiple sclerosis associated antigen;
(d) stimulating the T cells of step c) with the multiple sclerosis associated antigen;
(e) stimulating the T cells of step d) with a mitogen in the presence of IL-2;
(f) repeating steps d) and e) one or more times; and
(g) irradiating the T cells,
wherein the multiple sclerosis antigen consists of amino acids 83-99 of myelin basic protein and amino acids 151-170 of myelin basic protein.
8. The method of claim 7 wherein the plurality of mononuclear cells is obtained from the peripheral blood (PBMC) from said patient.
9. The method of claim 7 wherein the plurality of mononuclear cells is obtained from the cerebrospinal fluid (CSFMC) of the patient.
10. The method of claim 7 wherein IL-2 is added to the PBMCs in each of steps c), d), e) and f).
11. The method of claim 7 wherein said APCs are irradiated PBMCs obtained from the patient to be treated.
12. The method of claim 7 wherein the mitogen is selected from the group consisting of phytohemagglutinin, conconavalin A, pokeweed mitogen and monoclonal antibodies to CD3.