Induction of immune tolerance by using methotrexate

Abstract

The invention provides methods for reducing undesired immune responses, such as anti-drug antibody (ADA) responses and other T- and/or B-cell-mediated immune responses, in patients by using treatment with methotrexate.

1 : A method of inducing immune tolerance in a subject in need of treatment with a therapeutic, comprising administering to the subject an effective amount of methotrexate in a single cycle, thereby inducing immune tolerance toward the therapeutic in the subject. 
     
     
         2 - 6 . (canceled) 
     
     
         7 : The method of  claim 1 , wherein the therapeutic is a protein therapeutic. 
     
     
         8 - 10 . (canceled) 
     
     
         11 : The method of  claim 1 , wherein the subject is a human. 
     
     
         12 : The method of  claim 1 , wherein the therapeutic is an antibody therapeutic. 
     
     
         13 : The method of  claim 12 , wherein the antibody therapeutic is a monoclonal antibody therapeutic. 
     
     
         14 : The method of  claim 12 , wherein the antibody therapeutic is a lymphocyte-depleting agent. 
     
     
         15 : The method of  claim 13 , wherein the monoclonal antibody therapeutic is alemtuzumab. 
     
     
         16 : The method of  claim 15 , wherein the subject is a multiple sclerosis patient. 
     
     
         17 : The method of  claim 12 , wherein the antibody therapeutic is a polyclonal antibody therapeutic. 
     
     
         18 : The method of  claim 17 , wherein the polyclonal antibody therapeutic is polyclonal rabbit anti-thymocyte globulin antibody. 
     
     
         19 : The method of  claim 18 , wherein the subject is a human patient who is in need of organ transplantation, has aplastic anemia, and/or has or is at risk of having graft-versus-host disease. 
     
     
         20 : The method of  claim 1 , wherein the therapeutic is an enzyme. 
     
     
         21 : The method of  claim 20 , wherein the enzyme is human alpha-galactosidase A. 
     
     
         22 : The method of  claim 20 , wherein the enzyme is human acid alpha-glucosidase. 
     
     
         23 : The method of  claim 1 , wherein the effective amount is 0.1 mg/kg to 5 mg/kg. 
     
     
         24 : The method of  claim 1 , wherein the single cycle of methotrexate consists of 1 day of methotrexate administration or 2, 3, 4, 5, 6, 7, 8, 9, 10, or 11 consecutive days of methotrexate administration. 
     
     
         25 : The method of  claim 1 , wherein the single cycle of methotrexate is administered between 48 hours prior to and 48 hours after the onset of the therapeutic treatment. 
     
     
         26 - 53 . (canceled)