Isolation and characterization of a monoclonal antibody binding to the extracellular domain of the flk-2 tyrosine kinase receptor.
The flk-2 tyrosine kinase receptor is expressed on hematopoietic stem cells and on acute leukemias (AML and ALL). We have isolated a rat monoclonal antibody (71E1) that binds to this receptor with a relative affinity of 5 nM. The antibody immunoprecipitates both murine and human forms of flk-2 and can block receptor activation by its cognate ligand. In addition, 71E1 inhibits the in vitro proliferation of the murine leukemic cell line, M1, that expresses high levels of flk-2. These results suggest that 71E1 may have utility as both a reagent for elucidating the biological role of flk-2 in hematopoiesis and as an immunotherapeutic in the treatment of acute leukemias.
Rose
C
C
Molecular Biology Departments, ImClone Systems Inc., New York 10014, USA.
Rockwell
P
P
Yang
J Q
JQ
Pytowski
B
B
Goldstein
N I
NI
D016475:3T3 Cells; D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000302:isolation & purification*; D001666:Binding Sites, Antibody; D005110:Extracellular Space / Q000737:chemistry / Q000276:immunology; D006801:Humans; D015470:Leukemia, Myeloid, Acute; D051379:Mice; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma; D011518:Proto-Oncogene Proteins / Q000737:chemistry* / Q000276:immunology*; D051381:Rats; D011917:Rats, Inbred Lew; D020794:Receptor Protein-Tyrosine Kinases / Q000737:chemistry* / Q000276:immunology*; D014407:Tumor Cells, Cultured; D051941:fms-Like Tyrosine Kinase 3
D000911:Antibodies, Monoclonal; D011518:Proto-Oncogene Proteins; C497970:FLT3 protein, human; C497971:Flt3 protein, mouse; D020794:Receptor Protein-Tyrosine Kinases; D051941:fms-Like Tyrosine Kinase 3