Following an intensive course of combination chemotherapy, patients with minimal residual ovarian cancer were treated with increasing concentrations of intraperitoneal Corynebacterium parvum to assess whether or not natural killer (NK) cells could be activated. Immunotherapy was administered every 2 weeks, initially with a dose of 250 micrograms/m2, which was progressively escalated as tolerated. Each treatment induced a peritoneal cellular exudate which consisted primarily of neutrophils 48h after injection and of lymphocytes and macrophages at 7 and 14 days after injection. Peritoneal NK cytotoxicity increased during treatment in six of nine patients tested. NK precursor cells susceptible to in vitro activation with either C. parvum or interferon became detectable during treatment in all five patients tested. In four of these five, precursors were detected prior to the development of enhanced spontaneous NK activity. In four patients serially studied, peripheral blood NK activity increased during therapy. These results indicate that regional intraperitoneal therapy with C. parvum can enhance nonspecific antitumor cytotoxic mechanisms within the peritoneal cavity.
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