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 - 53 . (canceled) 
     
     
         54 . A method of increasing the efficacy of a therapeutic in a subject in need of treatment with the therapeutic, comprising administering to the subject an effective amount of methotrexate, thereby increasing the efficacy of the therapeutic in the subject. 
     
     
         55 . The method of  claim 54 , wherein the effective amount of methotrexate is administered in a single cycle. 
     
     
         56 . The method of  claim 55 , 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. 
     
     
         57 . The method of  claim 55 , wherein the single cycle of methotrexate is administered between 48 hours prior to and 48 hours after the onset of the therapeutic treatment. 
     
     
         58 . The method of  claim 54 , wherein the method comprises:
 a. inducing immune tolerance toward the therapeutic in the subject;   b. inhibiting antibody responses to the therapeutic in the subject;   c. alleviating an infusion reaction to the protein therapeutic in the subject;   d. reducing secondary autoimmunity in the subject;   e. increasing the percentage of T regulatory cells in the T cell population in the subject;   f. increasing the percentage of B regulatory cells in the B cell population in the subject; or   g. inhibiting T cell responses in the subject.   
     
     
         59 . The method of  claim 54 , wherein the subject is a human. 
     
     
         60 . The method of  claim 59 , wherein the subject is a multiple sclerosis patient, a patient who is in need of tissue transplantation, a patient who is in need of organ transplantation, a patient having aplastic anemia, or a patient having or is at risk of having graft-versus-host disease. 
     
     
         61 . The method of  claim 54 , wherein the therapeutic is a protein therapeutic. 
     
     
         62 . The method of  claim 61 , wherein the therapeutic is an antibody therapeutic. 
     
     
         63 . The method of  claim 62 , wherein the antibody therapeutic is a monoclonal antibody therapeutic. 
     
     
         64 . The method of  claim 62 , wherein the antibody therapeutic is a lymphocyte-depleting agent. 
     
     
         65 . The method of  claim 64 , wherein the antibody therapeutic is alemtuzumab 
     
     
         66 . The method of  claim 64 , wherein the monoclonal antibody therapeutic is rituximab. 
     
     
         67 . The method of  claim 62 , wherein the antibody therapeutic is a polyclonal antibody therapeutic. 
     
     
         68 . The method of  claim 67 , wherein the antibody therapeutic is polyclonal rabbit anti-thymocyte globulin antibody. 
     
     
         69 . The method of  claim 61 , wherein the therapeutic is an enzyme. 
     
     
         70 . The method of  claim 69 , wherein the enzyme is human alpha-galactosidase A. 
     
     
         71 . The method of  claim 69 , wherein the enzyme is human acid alpha-glucosidase. 
     
     
         72 . The method of  claim 54 , wherein the subject also receives another agent for immune modulation. 
     
     
         73 . The method of  claim 72 , wherein the agent for immune modulation is an immunosuppressant.