Methods for the treatment of autoimmune disorders using immunosuppressive monoclonal antibodies with reduced toxicity
The present invention provides methods of treating, preventing or ameliorating the symptoms of T cell-mediated immunological diseases, particularly autoimmune diseases, through the use of anti-CD3 antibodies. In particular, the methods of the invention provide for administration of antibodies that specifically bind the epsilon subunit within the human CD3 complex. Such antibodies modulate the T cell receptor/alloantigen interaction and, thus, regulate the T cell mediated cytotoxicity associated with autoimmune disorders. Additionally, the invention provides for modification of the anti-CD3 antibodies such that they exhibit reduced or eliminated effector function and T cell activation as compared to non-modified anti-CD3 antibodies.
1. A method of treating an autoimmune disorder or ameliorating the symptoms thereof in a patient in need thereof, said method comprising administering to said patient a therapeutically effective amount of an anti-CD3 antibody that has at least 50% reduced binding to at least one FcγR than an antibody with a wild type Fc domain, wherein said administration results in minimal toxicity;
wherein said treatment comprises a dosage regimen comprising doses of increasing amounts of said antibody on at least the initial 4 days of said dosage regimen;
wherein the dose on day 1 is 1.6 μg/kg, the dose on day 2 is 3.2 μg/kg, the dose on day 3 is 6.5 μg/kg, the dose on day 4 is 13 μg/kg, and the dose on any subsequent days is 26 μg/kg;
wherein said autoimmune disorder is type 1 diabetes; and
wherein said patient is in the early stages of disease when about 80% of β-cells have been destroyed.
2. The method of claim 1 , wherein said dosage regimen is 5 days or less.
3. The method of claim 1 , wherein said dosage regimen is 6 days or less.
4. The method of claim 1 , wherein said dosage regimen is 7 days or less.
5. The method of claim 1 , wherein said dosage regimen is 8 days or less.
6. The method of claim 1 , wherein said dosage regimen is 9 days or less.
7. The method of claim 1 , wherein said dosage regimen is 10 days or less.
8. The method of claim 1 , wherein said dosage regimen is 11 days or less.
9. The method of claim 1 , wherein said dosage regimen is 12 days or less.
10. The method of claim 1 , wherein said dosage regimen is 13 days or less.
11. The method of claim 1 , wherein said dosage regimen is 14 days or less.
12. The method of claim 1 wherein said patient is a child.