Selective in vitro and in vivo growth inhibition against human yolk sac tumor cell lines by purified antibody against human alpha-fetoprotein conjugated with mitomycin C via human serum albumin.
The anticancer drug mitomycin C (MMC) was conjugated with an affinity-purified horse antibody to human alpha-fetoprotein (aAFP) with human serum albumin (HSA) as the intermediate drug carrier. The conjugate (aAFP:HSA:MMC molar ratio, 1:1:30) retained full antibody binding activity as determined by a competitive binding radioimmunoassay. In a cytotoxicity test in which the AFP-producing human yolk sac tumor TG-1 cells were preincubated with test materials for 2 h followed by an additional 48-h culture in fresh medium, the conjugate was 20-fold more cytotoxic than free MMC at an equivalent MMC concentration of 100 ng/ml. The in vivo antitumor effect of the conjugate was tested against the human yolk sac tumor JOG-9 growing in athymic nude mice. When the tumor-bearing mice were treated with a total of 6 injections given on 2 consecutive days and then every other day starting 8 days after SC tumor inoculation [2 (equivalent MMC) microgram/head per injection], the conjugate retarded tumor growth more effectively than free MMC and normal horse immunoglobulin conjugate.
D000293:Adolescent; D000818:Animals; D000906:Antibodies / Q000008:administration & dosage*; D002460:Cell Line; D005260:Female; D006801:Humans; D008649:Mesonephroma / Q000188:drug therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D016685:Mitomycin; D008937:Mitomycins / Q000008:administration & dosage*; D010051:Ovarian Neoplasms / Q000188:drug therapy*; D012709:Serum Albumin / Q000008:administration & dosage*; D000509:alpha-Fetoproteins / Q000032:analysis / Q000276:immunology*
D000906:Antibodies; D008937:Mitomycins; D012709:Serum Albumin; D000509:alpha-Fetoproteins; D016685:Mitomycin