Antitumor activity against L1210 mouse leukemia of immunotoxins containing a monoclonal antibody to the glycolipid globotriaosylceramide.
Since immunotoxin (IT) containing the antiglobotriaosylceramide monoclonal antibody was found to be cytotoxic in murine L1210 leukemia cells, its potential antitumor activity could be evaluated in animals using the L1210 model. In vitro, L1210 cells incubated IT before grafting in DBA/2 mice failed to induce leukemia. All tumor cells were neutralized by IT. In animals, a significant but limited therapeutic effect on leukemic mice was obtained when IT was injected i.p. shortly after L1210 cell grafting. In contrast, no toxic effect of IT was observed in non-leukemic mice at doses far above those used in our therapeutic treatment. The potentiation effect of chloroquine on IT was moderated when a cloning efficiency assay was used, but 70% of the mice grafted with in vitro chloroquine-treated L1210 cells were cured with IT treatment.
D000818:Animals; D000918:Antibody Specificity; D002460:Cell Line; D002738:Chloroquine / Q000494:pharmacology; D005915:Globosides / Q000276:immunology*; D006017:Glycolipids / Q000276:immunology; D006028:Glycosphingolipids / Q000276:immunology*; D000922:Immunotoxins / Q000627:therapeutic use*; D007939:Leukemia L1210 / Q000628:therapy*; D051379:Mice; D008815:Mice, Inbred Strains; D009368:Neoplasm Transplantation; D012276:Ricin / Q000494:pharmacology; D014281:Trihexosylceramides
D005915:Globosides; D006017:Glycolipids; D006028:Glycosphingolipids; D000922:Immunotoxins; D014281:Trihexosylceramides; C018549:globotriaosylceramide; D002738:Chloroquine; D012276:Ricin