Production of human macrophages with potent antitumor properties (MAK) by culture of monocytes in the presence of GM-CSF and 1,25-dihydroxy vitamin D3.
Antitumoral macrophages (MAK) were obtained by the culture of human mononuclear cells in hydrophobic bags. From one cytapheresis, up to 10(9) mature macrophages could be purified by elutriation after one week of culture in IMDM medium in the presence of 2% human AB serum. These MAK cells were used for adoptive treatment in metastatic cancer patient with no dose-limiting toxicity. The present study aimed to improve the average MAK yield by addition of GM-CSF and of dihydroxy-cholecalciferol. The differentiated macrophages obtained presented higher antitumoral functionality in response to rh-IFN gamma than in their absence. These MAK presented all the differentiation antigens of cytotoxic macrophages compared to MAK cells differentiated in standard medium. They killed human tumor targets effectively in vitro at a low (1/1) effector/tumor ratio; furthermore, the antitumoral activity reached by MAK cells after IFN gamma activation appeared to be stabilized for several days.
Chokri
M
M
Centre National de Transfusion Sanguine, Les Ulis, Paris, France.
Lopez
M
M
Oleron
C
C
Girard
A
A
Martinache
C
C
Canepa
S
S
Siffert
J C
JC
Bartholeyns
J
J
D015703:Antigens, CD / Q000032:analysis; D002117:Calcitriol / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D006684:HLA-DR Antigens / Q000032:analysis; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D007700:Kinetics; D008262:Macrophage Activation / Q000187:drug effects; D008264:Macrophages / Q000187:drug effects / Q000276:immunology*; D009000:Monocytes / Q000187:drug effects / Q000276:immunology*; D011994:Recombinant Proteins; D014407:Tumor Cells, Cultured
D015703:Antigens, CD; D006684:HLA-DR Antigens; D011994:Recombinant Proteins; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D002117:Calcitriol