Absence of lysosomal cleavage in the cytotoxicity mechanism of an immunoconjugate composed of anti-alpha-fetoprotein monoclonal antibody and vindesine analog.
The effect of lysosomal enzyme inhibition on the cytotoxic activity of an immunoconjugate composed of anti-alpha-fetoprotein monoclonal antibody and vindesine analog (VDS) was studied in vitro using human tumor clonogenic assay (HTCA). Addition of the lysosome enzyme inhibitors, leupeptin and ammonium chloride, to the HTCA system had little influence on the cytotoxicity of this immunoconjugate. In separate experiments, no released VDS was detected by HPLC after incubation with the supernatant of rat liver homogenate without inhibitor. These results show that the immunoconjugate may bypass the lysosomal process and exert its activity as an intact or similar form.
Nagata
S
S
Shionogi Research Laboratories, Shionogi & Co., Ltd., Osaka, Japan.
Masuda
K
K
Nogusa
H
H
Hirano
K
K
Takagishi
Y
Y
D000643:Ammonium Chloride / Q000494:pharmacology; D000818:Animals; D000911:Antibodies, Monoclonal / Q000633:toxicity; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D017077:Culture Media, Conditioned; D004705:Endocytosis / Q000187:drug effects; D006801:Humans; D000922:Immunotoxins / Q000633:toxicity*; D007976:Leupeptins / Q000494:pharmacology; D008099:Liver / Q000378:metabolism; D008247:Lysosomes / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D014407:Tumor Cells, Cultured; D014751:Vindesine / Q000031:analogs & derivatives / Q000494:pharmacology*; D000509:alpha-Fetoproteins / Q000276:immunology
D000911:Antibodies, Monoclonal; D000972:Antineoplastic Agents, Phytogenic; D017077:Culture Media, Conditioned; D000922:Immunotoxins; D007976:Leupeptins; D000509:alpha-Fetoproteins; D000643:Ammonium Chloride; C032854:leupeptin; D014751:Vindesine