Method for improving the benefit of organ transplant
The invention relates to a method for improving the benefit of a therapy or a therapeutic agent to a subject. The method comprises administering to the subject an agent which reduces Fc receptor binding of serum IgG molecules in the subject; and subsequently administering said therapy or said therapeutic agent to the subject. The invention also relates to a method for reducing the effect of pathogenic autoantibodies in a subject, the method comprising (a) administering to the subject an agent which reduces Fc receptor binding of serum IgG molecules in the subject and optionally (b) subsequently subjecting the subject to a treatment which removes endogenous autoantibodies. The invention also relates to a kit for carrying out a method of the invention.
1. A method for improving the benefit to a human subject of a therapy, the method comprising (a) administering IgG-degrading-enzyme of Streptococcus pyogenes (IdeS) having IgG cysteine protease activity comprising or consisting of the amino acid sequence of SEQ ID NO: 1, or a conservative substitution IdeS variant thereof comprising an amino acid sequence having at least 90% sequence identity with SEQ ID NO: 1 which has IgG cysteine protease activity, to the subject; and (b) subsequently administering said therapy to the subject; wherein:
said therapy is an organ transplant;
the amount of said IdeS administered is between about 0.01 and about 0.24 mg/kg BW and is sufficient to eliminate Fc receptor binding by substantially all IgG molecules present in the serum of the subject; and
steps (a) and (b) are separated by a time interval which is sufficient for Fc receptor binding by substantially all IgG molecules present in the serum of the subject to be eliminated, and which interval is at most 6 hours.
2. The method according to claim 1 , wherein said variant of IdeS comprises an amino acid sequence having at least 95% identity of SEQ ID NO: 1.
3. The method according to claim 1 , wherein said IdeS protein is administered by intravenous infusion and the amount of said IdeS that is administered is around 0.24 mg/kg BW.
4. The method according to claim 1 , wherein:
the lower limit of the time interval between steps (a) and (b) is selected from: at least 30 minutes, at least 1 hour, at least 2 hours, at least 3 hours, at least 4 hours, at least 5 hours.
5. The method according to claim 1 , wherein the time interval between steps (a) and (b) is of 30 minutes to 1 hour, 30 minutes to 2 hours, 30 minutes to 3 hours, 30 minutes to 4 hours, 30 minutes to 5 hours, 30 minutes to 6 hours, 1 to 2 hours, 1 to 3 hours, 1 to 4 hours, 1 to 5 hours, 1 to 6 hours, 2 to 3 hours, 2 to 4 hours, 2 to 5 hours, 2 to 6 hours, 3 to 4 hours, 3 to 5 hours, 3 to 6 hours, 4 to 5 hours, 4 to 6 hours, or 5 to 6 hours.
6. The method according to claim 1 , wherein the organ is a kidney, liver, heart, pancreas, lung, or small intestine.
7. The method according to claim 6 , wherein the method also comprises a step conducted at or immediately prior to transplantation, which step comprises induction suppression of T cells and/or B cells in the patient.
8. The method according to claim 7 , wherein said induction suppression comprises administering an effective amount of at least one of Muromonab, Basiliximab, Daclizumab, an anti-thymocyte globulin (ATG) antibody, a lymphocyte immune globulin, anti-thymocyte globulin preparation (ATGAM), or Rituximab.
9. The method according to claim 1 , wherein the method comprises (a) administering IgG-degrading-enzyme of Streptococcus pyogenes (IdeS) having IgG cysteine protease activity consisting of the amino acid sequence of SEQ ID NO: 1.