Ligands to gm-csf or gm-csf-receptor for use in treatment of a haematologic malignancy in a patient having undergone allo-hct

Abstract

Described herein is the use of a non-agonist ligand, particularly an antibody, specifically binding to GM-CSF or one of CD116, CD131 and the GM-CSF receptor composed of CD116 and CD131 for use in treatment of leukemia in a patient having undergone allo-HCT or in treatment of other complications arising as a consequence of hematopoietic cell transplantation from an immunologically non-identical donor.

1 . A method for treating a patient suffering from or at risk of graft-versus-host-disease, and/or a haematologic malignancy, comprising:
 administering to the patient a non-agonist ligand specifically binding to granulocyte macrophage colony stimulating factor (GM-CSF), or at least one of CD116, CD131, or the GM-CSF receptor composed of CD116 and CD131,   
       thereby treating and/or inhibiting development of the graft-versus-host-disease, and/or treating a haematologic malignancy. 
     
     
         2 . The method of  claim 1 , wherein the patient has received an allogenic transplant. 
     
     
         3 . The method of  claim 2 , wherein the allogenic transplant is an allogeneic hematopoietic stem cell transfer (allo-HCT). 
     
     
         4 . The method of  claim 1 , wherein the haematologic malignancy is a leukaemia, lymphoma, or a multiple myeloma. 
     
     
         5 . The method of  claim 4 , wherein the leukaemia is selected from the group consisting of chronic myeloid leukemia (CML), acute myelogenous leukemia (AML), chronic lymphocytic leukemia (CLL), acute lymphocytic leukemia (ALL), and acute monocytic leukemia (AMoL). 
     
     
         6 . The method of  claim 4 , wherein the lymphoma is a Hodgkin lymphoma or a non-Hodgkin lymphoma. 
     
     
         7 . The method of  claim 1 , wherein the ligand is an antibody, antibody fragment, aptamer or antibody-like molecule. 
     
     
         8 . The method of  claim 7 , wherein the ligand is a human antibody or a humanized antibody, wherein the ligand is a neutralizing human antibody or a neutralizing humanized antibody. 
     
     
         9 . The method of  claim 8 , wherein the ligand is selected from the group consisting of mavrilimumab, namilumab, lenzilumab, otilimab, and gimsilumab. 
     
     
         10 . The method of  claim 9 , wherein the binding of the ligand to GM-CSF or one of CD116, CD131 and the GM-CSF receptor composed of CD116 and CD131 is characterized by a KD of smaller than (<) 10-7 moL-1, particularly wherein said binding is characterized by a KD of smaller than (<) 10-8 molL-1 or even (<) 10-9 molL-1. 
     
     
         11 . (canceled) 
     
     
         12 . A method for treating a patient in need of an allogenic transplant, and inhibiting the development or reducing the severity of associated graft versus host disease, the method comprising:
 providing the patient with an allogenic transplant; and   administering to the patient a non-agonist ligand specifically binding to granulocyte macrophage colony stimulating factor (GM-CSF), or at least one of CD116, CD131, the GM-CSF receptor composed of CD116 and CD131,   thereby inhibiting development or reducing the severity of the graft-versus-host-disease.   
     
     
         13 . The method of  claim 12 , wherein the allogenic transplant is an allogeneic hematopoietic stem cell transfer (allo-HCT), and wherein the allo-HCT is provided to the patient in a treatment for a haematologic malignancy. 
     
     
         14 . The method of  claim 12 , wherein the ligand is provided to the patient concurrently with or following the allogenic transplant. 
     
     
         15 . The method of  claim 13 , wherein the haematologic malignancy is a leukaemia selected from the group consisting of chronic myeloid leukemia (CML), acute myeloid leukemia (AML), chronic lymphocytic leukemia (CLL), acute lymphocytic leukemia (ALL), and acute monocytic leukemia (AMoL). 
     
     
         16 . The method of  claim 12 , wherein the ligand is an antibody, antibody fragment, aptamer or antibody-like molecule. 
     
     
         17 . The method of  claim 16 , wherein the ligand is selected from the group consisting of mavrilimumab, namilumab, lenzilumab, otilimab, and gimsilumab. 
     
     
         18 . A non-agonist polypeptide ligand specifically binding to granulocyte macrophage colony stimulating factor (GM-CSF), or at least one of CD116, CD131, or the GM-CSF receptor composed of CD116 and CD131. 
     
     
         19 . The ligand according to  claim 18 , wherein the ligand is an antibody, antibody fragment, aptamer or antibody-like molecule neutralizing the physiological function of GM-CSF or one of CD116, CD131 and the GM-CSF receptor composed of CD116 and CD131, respectively. 
     
     
         20 . The ligand according to  claim 19 , wherein the ligand is a human antibody or a humanized antibody, particularly wherein the ligand is a neutralizing human antibody or a neutralizing humanized antibody. 
     
     
         21 . The ligand according to  claim 20 , selected from Mavrilimumab, Namilumab, Lenzilumab, Otilimab, and Gimsilumab. 
     
     
         22 . The ligand according to  claim 21 , wherein the binding of the ligand to GM-CSF or one of CD116, CD131 and the GM-CSF receptor composed of CD116 and CD131 is characterized by a K D  of smaller than (<) 10 −7  molL-1, particularly K D <10 −8  molL-1, more particularly K D <10 −9  molL-1. 
     
     
         23 . A nucleic acid molecule encoding the ligand according to  claim 21 . 
     
     
         24 . The nucleic acid molecule according to  claim 23 , wherein the nucleic acid molecule is a DNA molecule or an RNA molecule. 
     
     
         25 . A nucleic acid expression construct comprising the nucleic acid molecule of  claim 23 . 
     
     
         26 . The nucleic acid expression construct according to  claim 25 , wherein the expression construct is selected from a DNA plasmid, a double stranded linear DNA, a single stranded RNA and a virus, wherein the virus is a lentivirus, a herpesvirus, an adenovirus or an adeno-associated virus. 
     
     
         27 . A pharmaceutical composition, comprising the ligand according to  claim 21 , a nucleic acid molecule encoding the ligand, or a nucleic acid expression construct comprising the nucleic acid molecule encoding the ligand; and a pharmaceutically acceptable carrier, wherein the pharmaceutical composition is formulated as an administration form for parenteral administration, more particularly for intravenous administration. 
     
     
         28 . (canceled) 
     
     
         29 . (canceled) 
     
     
         30 . (canceled) 
     
     
         31 . The pharmaceutical composition according to  claim 27  formulated as an administration form for intravenous administration.