Specific targeting of human hepatocellular carcinoma cells by immunoliposomes in vitro.
The monoclonal antibody AF-20 was raised against the human hepatocellular carcinoma (HCC) cell line FOCUS and binds with high affinity to a rapidly internalized 180-kd homodimeric glycoprotein that is abundantly expressed on the surface of human HCC and other human cancer cell lines. Immunoliposomes were produced by covalently coupling AF-20 to liposomes containing carboxyfluorescein. Interaction of immunoliposomes with various HCC cell lines in vitro was quantitatively assessed by flow cytometry and qualitatively analyzed by fluorescence microscopy. Liposomes bearing an isotype-matched nonrelevant monoclonal antibody (MAb) and cell lines not expressing AF-20 antigen served as controls. AF-20-immunoliposomes specifically bound to HCC and other human cancer cell lines expressing the AF-20 antigen and were rapidly internalized at 37 degrees C. Interaction of AF-20-conjugated liposomes with these cell lines was between 5 and 200 times greater than that of unconjugated liposomes, whereas no difference was observed between control liposomes bearing a nonrelevant antibody and unconjugated liposomes. Specificity of liposome-target cell interaction was confirmed by competitive inhibition assays. Kinetic analysis showed rapid association of AF-20 immunoliposomes with target cells, with saturation conditions being reached after 60 minutes. We conclude that the MAb AF-20 directs highly efficient, specific, and rapid targeting of immunoliposomes to human HCC and other human cancer cell lines in vitro. This targeted liposomal delivery system represents a promising approach for the development of immunotargeted diagnosis and therapy strategies against HCC.
Moradpour
D
D
Molecular Hepatology Laboratory, Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, USA.
Compagnon
B
B
Wilson
B E
BE
Nicolau
C
C
Wands
J R
JR
D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D000951:Antigens, Neoplasm / Q000276:immunology*; D006528:Carcinoma, Hepatocellular / Q000276:immunology / Q000628:therapy*; D004337:Drug Carriers; D005434:Flow Cytometry; D005456:Fluorescent Dyes; D006801:Humans; D018796:Immunoconjugates; D008081:Liposomes; D008113:Liver Neoplasms / Q000276:immunology / Q000628:therapy*; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D004337:Drug Carriers; D005456:Fluorescent Dyes; D018796:Immunoconjugates; D008081:Liposomes