Immunogenic agent therapy using plasmapheresis or exchange transfusion

1 . A method of reducing the immune response to an immunogenic therapeutic agent in a subject to whom the agent is administered wherein the agent contains at least one epitope foreign to the subject, comprising treating the subject with a blood antibody-depletion technique selected from the group consisting of plasmapheresis and exchange transfusion to lower the level of antibody or complement in blood of the subject prior to administering the agent;

wherein the plasmapheresis comprises:

(i) (a) obtaining from the subject blood which comprises cells and plasma, which plasma comprises antibodies or complement; (b) centrifuging the blood or filtering the blood with a filter, to isolate the plasma from the cells; and (c) returning the cells and not the plasma to the subject; or

(ii) (a) obtaining from the subject blood which comprises cells and plasma, which plasma comprises antibodies or complement; (b) filtering the blood with a first filter to separate the plasma from the cells, (c) returning the cells to the subject; (d) filtering the plasma isolated in step (b) with a second filter to deplete antibody or complement from the plasma; and (e) returning the depleted plasma to the subject.

2 . The method of claim 1 , wherein the blood antibody-depletion technique is plasmapheresis.

3 . The method of claim 1 , wherein the blood antibody-depletion technique is exchange transfusion.

4 . The method of claim 1 , wherein the agent is a therapeutic virus.

5 . The method of claim 4 , wherein the virus is an oncolytic virus.

6 . The method of claim 5 , wherein the oncolytic virus is a Newcastle Disease Virus.

7 . The method of claim 5 , wherein the oncolytic virus is a Vesicular Stomatitis Virus.

8 . The method of claim 5 , wherein the oncolytic virus is a reovirus.

9 . The method of claim 4 , wherein the virus is an adenovirus or a herpes virus.

10 . The method of claim 1 , wherein the agent is bacterial.

11 . The method of claim 10 , wherein the bacterial therapeutic agent is a Salmonella.

12 . The method of claim 11 , wherein the agent is a Salmonella typhimurium.

13 . The method of claim 10 , wherein the bacterial therapeutic agent is a Clostridium.

14 . The method of claim 10 , wherein the bacterial therapeutic agent is a Bifidobacterium.

15 . The method of claim 2 , wherein the plasmapheresis is performed up to twenty-four hours before administration of the agent.

16 . The method of claim 15 , wherein the plasmapheresis is performed up to six hours before administration of the agent.

17 . The method of claim 16 , wherein the plasmapheresis is performed up to one hour before administration of the agent.

18 . The method of claim 2 , wherein the plasmapheresis comprises: (a) obtaining from the subject blood which comprises cells and plasma, which plasma comprises antibodies or complement; (b) centrifuging the blood to isolate the plasma from the cells; and (c) returning the cells and not the plasma to the subject.

19 . The method of claim 2 , wherein the plasmapheresis comprises: (a) obtaining from the subject blood which comprises cells and plasma, which plasma comprises antibodies or complement; (b) filtering the blood with a filter to separate the plasma from the cells; and (c) returning the cells and not the plasma to the subject.

20 . The method of claim 19 , wherein the filter has a size cut-off of from 0.1 to 0.6 microns.

21 . The method of claim 18 or 19 , further comprising infusing into the bloodstream of the subject a plasma-replacement fluid in an amount approximately equivalent in volume to the plasma resulting from step (b), wherein the plasma-replacement fluid is not the plasma resulting from step (b) and the infusion is performed after any one or more of steps (a), (b) or (c).

22 . The method of claim 21 , wherein the plasma-replacement fluid is plasma from a source other than the subject.

23 . The method of claim 2 , wherein the plasmapheresis comprises: (a) obtaining from the subject blood which comprises cells and plasma, which plasma comprises antibodies or complement; (b) filtering the blood with a first filter to separate the plasma from the cells; (c) returning the cells to the subject; (d) filtering the plasma isolated in step (b) with a second filter to deplete antibody or complement from the plasma; and (e) returning the depleted plasma to the subject.

24 . The method of claim 21 , wherein the first filter has a size cut-off of from 0.1 to 0.6 microns.

25 . The method of claim 21 , wherein the second filter has a molecular freight cut-off of from 60 to 150 kilodaltons.

26 . The method of claim 1 , wherein the subject is a human.

27 . The method of claim 1 , wherein the subject is a non-human mammal.