REGRESSION OF ADVANCED OVARIAN-CARCINOMA BY INTRAPERITONEAL TREATMENTWITH AUTOLOGOUS T-LYMPHOCYTES RETARGETED BY A BISPECIFIC MONOCLONAL-ANTIBODY

Background: The high frequency of relapse after induction chemotherapy of advanced ovarian carcinoma calls for new therapeutic approaches, L ysis of ovarian carcinoma cells can be achieved by retargeting of T ly mphocytes using F(ab')(2) fragments of the bispecific monoclonal antib ody (MAb) OC/TR, which is directed to the CD3 molecule on T lymphocyte s and to the folate receptor on ovarian carcinoma cells, Purpose: Our purpose was to assess in ovarian carcinoma patients the antitumor acti vity of in vitro-activated autologous peripheral blood T lymphocytes r etargeted with OC/TR, Methods: Patients with epithelial ovarian cancer (International Federation of Gynecology and Obstetrics stages III and IV) meeting specific criteria were eligible to enter a phase II immun otherapy trial, Before immunotherapy, the 28 patients who entered the trial underwent laparotomy to reduce their tumor load and to allow mea surement of all indicator lesions, They then received two cycles of fi ve daily intraperitoneal infusions of autologous in vitro activated pe ripheral blood T lymphocytes retargeted with OC/TR plus recombinant in terleukin 2 (IL-2) with (n = 11) or without (n = 17) a second daily in fusion of OC/TR F(ab')(2) and IL-2, Response to treatment could be ass essed in 26 patients following explorative laparotomy; time to progres sion could be assessed in 27 patients, Results: Seven patients had cli nical evidence of progressive disease after treatment and therefore di d not undergo laparotomy, Of the 19 patients evaluated by surgery and histology, three showed complete response, one showed complete intrape ritoneal response with progressive disease in retroperitoneal lymph no des, three showed partial response, seven had stable disease, and five had progressive disease, The overall intraperitoneal response rate wa s 27% (95% confidence interval [CI] = 10%-44%), The complete responses seen in three patients lasted 26 months in one patient, 23 months in the second, and 18 months in the third, Two patients were not assessab le for response, One of these patients had bowel perforation during ca theter removal, which precluded further evaluation, The second patient was positive only by cytologic examination before immunotherapy, was tumor free at laparotomy after immunotherapy, and remained so for the entire 21 months of follow-up, as determined by cytologic examination of random biopsy specimens, The median time to disease progression in the 15 assessable patients plus those who had stable disease was 11 mo nths (95% CI = 6-18 months), Immunotherapy-related toxic effects inclu ded mild to moderate fever, nausea, emesis, and fatigue, Anti-mouse an tibodies were detectable by the end of the treatment in 21 of 25 patie nts tested, Conclusions: Locoregional immunotherapy of ovarian cancer with bispecific MAb-retargeted T lymphocytes can result in tumor regre ssion, Toxicity was mild to moderate and only transient, Implications: Improvement in systemic antitumor responses is needed before this app roach can prove useful as adjunctive treatment following induction che motherapy in patients with minimal residual disease.