[Antitumor effect of adriamycin entrapped in liposomes conjugated with anti-human alpha-fetoprotein or anti-carcinoembryonic antigen monoclonal antibodies].
Monoclonal antibodies against human alpha-fetoprotein (AFP) or carcinoembryonic antigen (CEA) were conjugated to liposomes containing adriamycin (ADM), and the therapeutic effects of the conjugates were experimentally studied in vitro and in vivo. The liposomes were prepared from a lipid mixture of egg phosphatidyl choline, cholesterol and dipalmitoylphosphatidyl ethanolamine, and were covalently coupled with anti-AFP monoclonal antibody (19-F-12) or anti-CEA monoclonal antibody (1-C-11) after activation of antibody with the N-hydroxysuccinimidyl 8-(2-pyridyldithio) propionate and dithiothreitol. The selective binding of the 19-F-12 conjugated liposomes to AFP-positive human hepatoma cell line PLC and the 1-C-11 conjugated liposomes to CEA-positive colon cancer cell line C-1 as demonstrated using fluorescent liposomes. In vitro studies with PLC and C-1 clearly indicated that monoclonal antibody-conjugated liposomes containing ADM exerted much more effects than unconjugated liposomes containing ADM on target cells in the inhibition assay of [3H]-thymidine incorporation. The therapeutic effects of the conjugates were tested in vivo on AFP-positive human hepatoma xenograft, Li-7, and CEA-positive human colon cancer xenograft, Co-4, maintained in BALB/c nu/nu mice. The antitumor effect of the antibody-conjugated liposomes containing ADM was far greater than that of unconjugated liposomes containing ADM or that of ADM alone as assessed by tumor weight and histological findings.
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D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000627:therapeutic use*; D002272:Carcinoembryonic Antigen / Q000276:immunology*; D002455:Cell Division; D004317:Doxorubicin / Q000627:therapeutic use*; D006801:Humans; D008081:Liposomes / Q000008:administration & dosage*; D051379:Mice; D009374:Neoplasms, Experimental / Q000473:pathology / Q000628:therapy*; D000509:alpha-Fetoproteins / Q000276:immunology*
D000911:Antibodies, Monoclonal; D002272:Carcinoembryonic Antigen; D008081:Liposomes; D000509:alpha-Fetoproteins; D004317:Doxorubicin