Anti-GM-CSF monoclonal antibody therapy for refractory acute leukemia.
Several phase I trials and pilot studies using Monoclonal Antibody (MoAb) have been performed in B-cell neoplasms, but this approach has not until now been extensively tested in myeloid leukemias. Recently, we evaluated the use of anti-Granulocyte-Macrophage Colony-Stimulating Factor MoAb (Anti-GM-CSF MoAb) in acute myeloid leukemia (AML). Eight patients fulfilled inclusion criteria and received a single course of Anti-GM-CSF MoAb infusion during 5 to 15 days. Anti-GM-CSF MoAb was well tolerated and was detectable in pharmacokinetics studies. Using Human Anti-Rat Antibodies (HARA), we also observed an immunological response to the MoAb. Despite sufficient levels detected in the serum and biological activity of Anti-GM-CSF MoAb in vivo, no anti-leukemic effect was noted, except for one patient who had a decrease of 50% in the marrow blast cell mass. These observations indicate that leukemic proliferation in vivo involves a complex network spanning many mechanisms, and inhibition of leukemia is not effective if only one of these key targets is attacked. The development of these new approaches may be more effective in the future.
Department of Haematology, Institut Paoli-Calmettes, Marseille, France.
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R
Bouabdallah
D
D
Olive
P
P
Meyer
M
M
Lopez
D
D
Sainty
M
M
Hirn
P
P
Mannoni
E
E
Fougereau
J A
JA
Gastaut
D
D
Maraninchi
D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001792:Blood Platelets / Q000187:drug effects; D004912:Erythrocytes / Q000187:drug effects; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000276:immunology*; D006801:Humans; D007116:Immunization, Passive; D016756:Immunoglobulins, Intravenous / Q000493:pharmacokinetics / Q000627:therapeutic use*; D015470:Leukemia, Myeloid, Acute / Q000097:blood / Q000473:pathology / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects
D000911:Antibodies, Monoclonal; D016756:Immunoglobulins, Intravenous; D016178:Granulocyte-Macrophage Colony-Stimulating Factor