Preparation and antitumor effect of macrophage activating factor (MAF) encapsulated in liposomes bearing a monoclonal anti-human melanoma (A375) antibody.
We prepared large unilamellar vesicles containing the cell-free culture supernatant of a human T cell hybridoma rich in macrophage activating factor (MAF) and bearing monoclonal antibodies against human melanoma A375 tumor cells; their antitumor activity against A375 cells was examined in vitro and in vivo. Both MAF-immunoliposomes (bearing antibodies) and MAF liposomes (not bearing antibodies) showed macrophage-mediated cytotoxicity in vitro at a high E/T ratio (about 40). But at a low E/T ratio (about 15), only MAF-immunoliposomes showed tumoricidal activity, their activity being more than ten thousand-fold stronger compared with a soluble MAF preparation (MAF solution). MAF-immunoliposomes not only showed tumor neutralization mediated by macrophages in vivo when a mixture of tumor cells, macrophages, and MAF-immunoliposomes was locally injected, but also showed significant inhibition of tumor growth on repeated i.v. systemic administration of them. On the other hand, other samples (MAF-liposomes without the antibody, a MAF solution, and immunoliposomes without MAF) were not significantly effective against tumor growth. These results may constitute evidence that the delivery of lymphokines to the tumor sites is important or even critical when an attempt is made to treat cancer with lymphokines with the expectation of the potentiation of the host's immune system.
Watanabe
Y
Y
Division of Chemical Toxicology and Immunochemistry, Faculty of Pharmaceutical Sciences, University of Tokyo, Japan.
Uchida
E
E
Higuchi
M
M
Imai
Y
Y
Osawa
T
T
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000276:immunology; D003602:Cytotoxicity, Immunologic; D005260:Female; D008081:Liposomes / Q000008:administration & dosage*; D008222:Lymphokines / Q000008:administration & dosage / Q000494:pharmacology*; D016215:Macrophage-Activating Factors; D008264:Macrophages / Q000276:immunology; D008545:Melanoma / Q000276:immunology* / Q000628:therapy; D051379:Mice; D008807:Mice, Inbred BALB C; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D008081:Liposomes; D008222:Lymphokines; D016215:Macrophage-Activating Factors