Antitumor effect of adriamycin entrapped in liposomes conjugated with anti-human alpha-fetoprotein monoclonal antibody.
The monoclonal antibody, 19-F-12 (IgG2b), against human alpha-fetoprotein was conjugated to liposomes containing Adriamycin, and the therapeutic effects of the conjugate were experimentally studied using the alpha-fetoprotein-producing human hepatoma strain, Li-7, maintained in BALB/c nu/nu male mice. Three i.v. injections of liposomes containing Adriamycin (7.5 mg/kg) into tumor-bearing mice significantly inhibited the tumor growth, and the therapeutic effect of the antibody-conjugated liposomes was greater than that of unconjugated liposomes, as judged from the tumor weights and histological findings. Furthermore, the experiments were repeated with Adriamycin (4-5 mg/kg) in free form, since administration of Adriamycin (7.5 mg/kg) in free form was highly toxic for the mice. The results still indicated that the therapeutic effect of Adriamycin in 19-F-12 conjugated liposomes was superior to that of free Adriamycin or Adriamycin in unconjugated liposomes. In contrast to the treatment for Li-7 in nude mice, the therapeutic effect of Adriamycin in 19-F-12 conjugated liposomes was not much different from that of Adriamycin in normal mouse IgG (IgG2b fraction) conjugated liposomes against alpha-fetoprotein-negative human breast cancer strain MX1. Tissue distribution studies after i.v. injection of Adriamycin in various forms into mice revealed that preferential delivery of Adriamycin to tumors occurred to some extent with antibody-conjugated liposomes as compared to the unconjugated liposomes. In addition, reduction of the distribution of Adriamycin to the heart was achieved by administering the drug in the liposome-entrapped form, and this enabled the use of a higher dose (7.5 mg/kg) of Adriamycin without toxic side effect.
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000276:immunology*; D004317:Doxorubicin / Q000008:administration & dosage* / Q000378:metabolism / Q000627:therapeutic use; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000276:immunology; D008081:Liposomes / Q000008:administration & dosage*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009369:Neoplasms / Q000628:therapy*; D014018:Tissue Distribution; D000509:alpha-Fetoproteins / Q000276:immunology*
D000911:Antibodies, Monoclonal; D007140:Immunoglobulin Fab Fragments; D008081:Liposomes; D000509:alpha-Fetoproteins; D004317:Doxorubicin