Restoration of interferon alpha potentiation of a recombinant ricin A chain immunotoxin following cytoreduction of xenografts of advanced ovarian tumors

Background: We have demonstrated that, in the human ovarian carcinoma cell line (OVCAR-3), recombinant human interferon [alpha] (rHuIFN-[alpha]) potentiated in vitro inhibition of protein synthesis by immunotoxins. The antitumor activity of intracavitary immunotoxin administered to nude mice 5 days after tumor cell injection was enhanced by a nontherapeutic dose of rHuIFN-[alpha], as evidenced by increased survival time. Purpose: Our purpose was to determine the outcome of treatment with immunotoxin and rHuIFN-[alpha] in xenografts of more advanced tumors. Methods: At 10 or 15 days after tumor cell injection, nude mice with peritoneal OVCAR-3 xenografts were treated intraperitoneally with immunotoxin or with 454A12 monoclonal antibody (Mab) recombinant ricin A chain (rRA), alone or combined with a nontherapeutic dose of rHuIFN-[alpha]. The immunotoxin was composed of rRA covalently bound to an anti-CD71 (transferrin receptor) MAb. In other experiments, mice were treated intraperitoneally with cyclophosphamide and cisplatin to reduce tumor size on days 20 and 27 after tumor cell inoculation and then, beginning on day 40, with immunotoxin alone or combined with rHuIFN-[alpha]. Results: Initiation of treatment 10 days after OVCAR-3 transplantation significantly increased median survival from 41 to 89 days (10% survivors on day 120) with 454A12 MAb rRA alone and to more than 120 days (70% survivors) with 454A12 MAb rRA combined with rHuIFN-[alpha] (P