LOCAL BUT NO SYSTEMIC IMMUNOMODULATION BY INTRAPERITONEAL TREATMENT OF ADVANCED OVARIAN-CANCER WITH AUTOLOGOUS T-LYMPHOCYTES RE-TARGETED BYA BI-SPECIFIC MONOCLONAL-ANTIBODY

We have reported a 27% overall anti-tumor response using i.p. immunoth erapy of advanced ovarian carcinoma with autologous, ex vivo expanded, T lymphocytes re-targeted with bi-specific monoclonal antibody OC/TR, combined with soluble OC/TR and low-dose recombinant interleukin-2 (I L-2). This treatment had no effect on extraperitoneal disease. Therefo re we studied in 13 patients whether this immunotherapeutic protocol r esulted only in local or also in systemic immunomodulation. The phenot ype of the ex vivo expanded lymphocytes was mainly CD3(+), 4(-), 8(+), 16(-), 56(-). Their OC/TR-re-targeted cytolytic activity against Igro v-1 ovarian-carcinoma cells was approximately as high in responders as in non-responders. Following most therapeutic cycles, the immunopheno type of lymphocytes recovered from the peritoneal fluid was similar to that of the infused T cells (i.e., mainly CD3(+), 4(-), 8(+)) and the y were coated with OC/TR. However, cytolytic activity of the recovered lymphocytes against Igrov-1 cells was low in direct assays, and only slightly increased after additional in vitro re-targeting with OC/TR. Systemically, the i.p. immunotherapy resulted in a transient lymphopen ia lasting for about 7 days, low (i.e., 5 to 13 ng/ml) serum concentra tions of free, functional OC/TR, and very weak coating of circulating T lymphocytes with OC/TR. These peripheral-blood T lymphocytes did not exert OC/TR-re-targeted cytolytic activity. Thus, locoregional OC/TR- re-targeted cellular immunotherapy resulted in substantial local immun omodulation and anti-tumor effects but virtually no systemic immunomod ulation. (C) 1997 Wiley-Liss, Inc.