Effect of virus-modified tumor cell extracts, autologous mononuclear cell infusions and interleukin-2 on oncolytic activity of effector cells of patients with advanced ovarian cancer.

We studied the biological responses of six ovarian cancer patients after intraperitoneal (i.p.) injections of virus-modified tumor cell extracts (VMTE) and autologous peripheral blood mononuclear cells, collected by leukapheresis after two injections of VMTE. VMTE was prepared from allogeneic ovarian cell lines, OV2774 and CaOV3, modified by influenza virus, A/PR8/34. A dose of 9 mg VMTE was given i.p. in total of 2-4 injections, and (1-9) x 10(8) autologous mononuclear cells were infused i.p., 24 h after the second VMTE injection, and 24 h and 72 h after the third VMTE injection. Both peripheral blood (PB) and peritoneal cavity (PC) effector cell cytotoxicity was significantly enhanced against the K562 cell line in the majority of patients, 24-48 h after the second and third VMTE injections. This was accompanied by a dramatic influx of neutrophils into PC (57-550-fold), increase in absolute numbers of lymphocytes, (including large granular lymphocytes) and monocytes, and resulted also in a significant decrease in the number of ascitic tumor cells (98% reduction). The infusion of autologous mononuclear cells did not appear to influence either cytotoxicity or cell infiltration of the peritoneal cavity. We also investigated the in vitro effect of recombinant interleukin-2 (IL-2) on effector cells from PB and PC from patients before and after VMTE treatment. Cytotoxicity of both of these compartments was significantly potentiated after culture with IL-2. In three out of five VMTE-treated patients, PC cytotoxicity was significantly higher after activation with IL-2 than that of patients before VMTE treatment. These data suggest that VMTE induces regional cellular immunity, which could be further potentiated by culture of PC effector cells with IL-2. Thus, combination of VMTE and IL-2 after regional administration could represent the effective therapy for patients with advanced ovarian cancer.