Immunotoxins to the murine transferrin receptor: intracavitary therapy of mice bearing syngeneic peritoneal tumors.

Two rat monoclonal antibodies to the murine transferrin receptor (TFR) were each conjugated to recombinant ricin toxin A chain (rRTA). The monoclonal antibodies, R17 217 and YE1/9.9, bound to partially overlapping antigenic determinants on the murine TFR that were distinct from the transferrin binding site. Immunotoxins R17 217-rRTA and YE1/9.9-rRTA were potent cytotoxins for mouse cell lines in vitro. Animal toxicity studies showed that they were 10 to 20 times more toxic to mice than were control immunotoxins, including the anti-human-TFR immunotoxin 454A12-rRTA. The mouse toxicity of i.p. injected R17 217-rRTA could be partially blocked by the i.p. or i.v. administration of unconjugated R17 217 monoclonal antibody. I.p. but not i.v. administration of antimouse-TFR immunotoxins prolonged the survival of mice given implants of syngeneic peritoneal P388D1 lymphoid tumors. The anti-mouse-TFR immunotoxins killed at least 99.9% of the P388D1 tumor cells in vivo. In addition, i.p. treatment with immunotoxin R17 217-rRTA was able to prolong the survival of mice given an implant of a murine ovarian teratocarcinoma. The results show that anti-TFR immunotoxins can be efficacious in homologous species when the tumor is confined to a specific body cavity and immunotoxin can be delivered into that cavity.