[Anti-tumor activity of an anti-human alpha-fetoprotein antibody-human serum albumin-mitomycin C conjugate against human yolk sac tumor maintained in vitro and in nude mice in vivo].
The anti-cancer drug, mitomycin C (MMC), was conjugated to an affinity-purified horse antibody to human alpha-fetoprotein (aAFP) via purified human serum albumin (HSA) as an intermediate carrier. The conjugate (aAFP immunoglobulin (IgG): HSA: MMC, molar ratio 1: 1.10:29.8) was 21 or 38 times as cytotoxic as free MMC or PBS at the MMC concentration of 100 ng/ml, respectively, against alpha-fetoprotein-producing human yolk sac tumor in vitro. The in vivo effects of the conjugate and various controls were also tested against human yolk sac tumor growing in nude mice. The conjugate over a total of 6 injections retarded the initial tumor growth at the concentration of MMC, containing equivalent amounts of 2 micrograms/mouse (0.1 mg/kg)/injection in the conjugate, whereas free MMC and normal horse IgG-HSA-MMC showed only slight inhibitory effects alone at non-toxic levels. These results suggest that the specific antibody-conjugate was considerably more effective than free MMC against the tumor maintained in nude mice as well as in vitro cultures.
K
K
Ohkawa
Y
Y
Tsukada
N
N
Umemoto
T
T
Hara
D000818:Animals; D000906:Antibodies / Q000008:administration & dosage*; D000918:Antibody Specificity; D003602:Cytotoxicity, Immunologic; D005260:Female; D006801:Humans; D008649:Mesonephroma / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D051379:Mice; D008819:Mice, Nude; D016685:Mitomycin; D008937:Mitomycins / Q000008:administration & dosage*; D009368:Neoplasm Transplantation; D010051:Ovarian Neoplasms / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D012709:Serum Albumin / Q000276:immunology*; D000509:alpha-Fetoproteins / Q000276:immunology*
D000906:Antibodies; D008937:Mitomycins; D012709:Serum Albumin; D000509:alpha-Fetoproteins; D016685:Mitomycin