Intraperitoneal recombinant gamma-interferon in patients with recurrent ascitic ovarian carcinoma: modulation of cytotoxicity and cytokine production in tumor-associated effectors and of major histocompatibility antigen expression on tumor cells

Seven patients with advanced epithelial carcinoma and ascites, relapsing after two or more regimens of standard chemotherapy, have been treated with recombinant gamma-interferon (rIFN-gamma) i.p., via a permanent catheter. rIFN-gamma (Immuneron; Biogen; 0.5 mg = 10(7) IU in 2 liters of saline) was administered 3 times a week, on alternate weeks, for a total of nine courses. No major toxicities were observed: mild fever, malaise, and a flu-like syndrome occurred in all patients. The modulation of immunological parameters was studied. Cytotoxic activity of immunocompetent cells against tumor cell lines was measured both in the peritoneal compartment and in peripheral blood mononuclear cells. A significant increase of cytotoxicity of tumor-associated macrophages was observed in 5 of 7 patients and in 4 of 7 patients with tumor-associated peritoneal lymphocytes. Circulating effector cells were only occasionally stimulated. Tumor-associated macrophages isolated from the ascitic fluid and stimulated with lipopolysaccharide produced higher amounts of interleukin 1 in 5 of 6 patients tested, while interleukin 6 production by unstimulated tumor-associated macrophages was augmented in 2 of 2 patients after rIFN-gamma treatment. Freshly isolated ovarian carcinoma cells from the ascitic fluid has a variable, although usually low, expression of HLA-DR antigens. rIFN-gamma treatment caused a marked increase in HLA-DR expression in all patients tested. Expression of HLA class I antigens was negative in 2 of 5 patients and was strongly increased in 1 of the 2 after treatment. The observation that rIFN-gamma administered i.p. activates in situ effector cells and augments major histocompatibility antigen expression in tumor cells, with minimal toxicity, encourages further efforts to investigate its therapeutic potential in ovarian carcinoma.