Control of the antitumoral activity of human macrophages produced in large amounts in view of adoptive transfer.
Purified human blood monocytes were grown in hydrophobic bags in RPMI medium containing additional amino acids, indomethacine and growth factors. Autologous serum was added after a few days of culture at 37 degrees C, 5% CO2. The antitumoral activity generated by activated monocytes against human tumor cells grown in vitro was mediated by soluble effectors in contrast to macrophages which acted by cell contact. Monocyte differentiation into macrophages was achieved after 7 days of culture and characterized by phagocytosis and expression of MAX 1 antigen and non-specific esterases. The macrophages remaining in suspension in the bags were activated by exposure to immunostimulating compounds used alone or in combination (recombinant human gamma-interferon and muramyldipeptide). Activated macrophages were cytotoxic in vitro against U 937 or ovary carcinoma tumor lines (95% cytotoxicity) at a 1/1 effector/tumor cell ratio. The antitumoral potency of activated macrophages was confirmed in vivo where adoptive transfer of one million human macrophages twice a week to nude mice bearing human ovary carcinoma caused a marked regression of the primary tumor.
Dumont
S
S
Département d'Immunologie et d'Immunopharmacologie, UER de Pharmacie, Université Louis Pasteur, Illkirch-Graffenstaden, France.
Hartmann
D
D
Poindron
P
P
Oberling
F
F
Faradji
A
A
Bartholeyns
J
J
D000818:Animals; D000943:Antigens, Differentiation / Q000032:analysis; D043182:Carboxylesterase; D002265:Carboxylic Ester Hydrolases / Q000378:metabolism; D002454:Cell Differentiation; D003602:Cytotoxicity, Immunologic; D005260:Female; D006801:Humans; D007116:Immunization, Passive; D008262:Macrophage Activation; D008264:Macrophages / Q000201:enzymology / Q000276:immunology*; D051379:Mice; D008819:Mice, Nude; D009000:Monocytes / Q000276:immunology; D010051:Ovarian Neoplasms / Q000628:therapy; D010587:Phagocytosis; D014407:Tumor Cells, Cultured / Q000276:immunology*
D000943:Antigens, Differentiation; D002265:Carboxylic Ester Hydrolases; D043182:Carboxylesterase