Methods for treating and/or preventing graft-versus-host disease and/or diffuse alveolar hemorrhage and/or veno-occlusive disease associated with hematopoietic stem cell transplant
In one aspect, the invention provides methods of inhibiting the effects of MASP-2-dependent complement activation in a human subject suffering from graft-versus-host disease and/or diffuse alveolar hemorrhage and/or veno-occlusive disease associated with a hematopoietic stem cell transplant. The methods comprise the step of administering, to a subject in need thereof, an amount of a MASP-2 inhibitory agent effective to inhibit MASP-2-dependent complement activation.
1. A method of treating a human subject suffering from, or at risk for developing, diffuse alveolar hemorrhage associated with hematopoietic stem cell transplant, the method comprising administering to the subject a composition comprising an amount of a MASP-2 inhibitory antibody, or antigen-binding fragment thereof, effective to inhibit MASP-2-dependent complement activation.
2. The method of claim 1 , wherein the MASP-2 inhibitory antibody is a monoclonal antibody, or fragment thereof that specifically binds to human MASP-2.
3. The method of claim 1 , wherein the antibody or fragment thereof is selected from the group consisting of a recombinant antibody, an antibody having reduced effector function, a chimeric antibody, a humanized antibody, and a human antibody.
4. The method of claim 1 , wherein the MASP-2 inhibitory antibody does not substantially inhibit the classical pathway.
5. The method of claim 1 , wherein the MASP-2 inhibitory antibody inhibits C3b deposition in 90% human serum with an IC 50 of 30 nM or less.
6. The method of claim 1 , wherein the MASP-2 inhibitory antibody is delivered to the subject systemically.
7. The method of claim 1 , wherein the method further comprises identifying a human subject suffering from, or at risk for developing diffuse alveolar hemorrhage prior to the step of administering to the subject a composition comprising an amount of a MASP-2 inhibitory antibody, or antigen-binding fragment thereof, effective to inhibit MASP-2-dependent complement activation.
8. The method of claim 1 , wherein the subject has previously undergone, or is currently undergoing, or will undergo a hematopoietic stem cell transplant.
9. The method of claim 1 , wherein the MASP-2 inhibitory antibody or antigen-binding fragment thereof, comprises a heavy chain variable region comprising CDR-H1, CDR-H2 and CDR-H3 of the amino acid sequence set forth as SEQ ID NO:67 and a light chain variable region comprising CDR-L1, CDR-L2 and CDR-L3 of the amino acid sequence set forth as SEQ ID NO:70.
10. The method of claim 1 , wherein the subject has received a hematopoietic stem cell transplant.