Methods for treating progressive multifocal leukoencephalopathy (PML)
View Patent ↗The present invention relates generally to the treatment of PML by infusion of activated and expanded autologous lymphocytes.
1. A method for treating Progressive Multifocal Leukoencephalopathy comprising administering to a patient a population of T cells activated and expanded according to a method comprising,
(a) activating a population of T cells in vitro with an agent which stimulates a TCR/CD3 complex-associated signal in the T cells, wherein the agent is attached on a surface, wherein the agent is an anti-CD3 antibody or antigen-binding fragment thereof; and
(b) stimulating a CD28 accessory molecule on the surface of the T cells in vitro with a ligand that binds the CD28 accessory molecule on the surface of the T cells, wherein the ligand is attached on the same surface as the agent; the activating and stimulating steps thereby inducing proliferation of the T cells.
2. The method of claim 1 wherein the ligand is selected from the group consisting of an anti-CD28 antibody, or antigen-binding fragment thereof, B7-1 or a CD28-binding fragment thereof, and B7-2 or a CD28-binding fragment thereof.
3. The method of claim 1 wherein the surface is selected from the group consisting of a bead, a lipid bilayer, a cell surface, and a tissue-culture dish.
4. The method of claim 1 wherein the activated and expanded T cells are administered intravenously.
5. The method of claim 3 wherein said cell surface is of a human cell line.
6. The method of claim 5 wherein said human cell line is K562.
7. The method of claim 5 wherein said cell is genetically modified to express a human Fcγ receptor.
8. The method of claim 7 wherein said human Fcγ receptor comprises CD32 or CD64.
9. The method of claim 5 wherein said cell is further genetically modified to express a co-stimulatory molecule selected from the group consisting of CD80, CD86, 4-1BBL, OX40L, ICOS-L, ICAM, PD-L1 and PD-L2.
10. The method of claim 5 wherein said cell has been modified to express a cytokine.
11. The method of claim 10 wherein said cytokine is selected from the group consisting of IL-2, GM-CSF, IL-4, TNF-α, and IFN-γ.
12. A method for treating a patient at risk of having Progressive Multifocal Leukoencephalopathy (PML) wherein said patient has undergone therapy that raises the risk for the development of PML, the method comprising administering to a patient a population of T cells activated and expanded according to a method comprising,
(a) activating a population of T cells in vitro with an agent which stimulates a TCR/CD3 complex-associated signal in the T cells, wherein the agent is attached on a surface; and
(b) stimulating a CD28 accessory molecule on the surface of the T cells in vitro with a ligand that binds the CD28 accessory molecule on the surface of the T cells, wherein the ligand is attached on the same surface as the agent; the activating and stimulating steps thereby inducing proliferation of the T cells.