Intraperitoneal administration of human recombinant interferon-alpha in patients with ovarian cancer: effects on lymphocyte phenotype and cytotoxicity.

Eleven patients with persistent Stage III ovarian cancer, documented at second look laparotomy, received i.p. human recombinant interferon-alpha (5-50 x 10(6) units/week). Prior to immunotherapy, patients' peritoneal cell lymphocytes (PCLs) contained decreased proportions of Leu-7+ and Fc-receptor+ cells and almost nondetectable natural killer (NK) and antibody-dependent cell cytotoxic (ADCC) activity. In contrast, patients' peripheral blood lymphocytes (PBLs) contained normal proportions of lymphocyte subsets and cytotoxic activity compared to control donor PBLs. During therapy, there was a concurrent increase in PCL Leu-7+ cells and NK lysis. Both peaked predictably at 24 h after each treatment, regardless of the dose injected, and usually returned to baseline by Day 7 of each weekly cycle. PCL NK enhancement was striking, usually increasing from 2-6% (effector:target ratio, 25:1) to over 30% lysis. Enhancement of PCL ADCC was less impressive. PCLs of several patients developed lytic activity towards NK-resistant Raji targets. During therapy, patients' PBLs demonstrated: (a) modestly enhanced NK lysis at Day 4 of each cycle, and; (b) no development of Raji lysis. These data clearly demonstrate the efficacy of i.p. interferon in activation of peritoneal NK activity. However, increased NK lysis did not correlate with individual tumor responses in this cohort of patients.