We have reported a 27% overall anti-
tumor response using i.p.
immunotherapy 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 (IL-2). This treatment had no effect on extraperitoneal disease. Therefore we studied in 13 patients whether this immunotherapeutic protocol resulted only in local or also in systemic
immunomodulation. The phenotype of the ex vivo expanded lymphocytes was mainly CD3+, 4-, 8+, 16-, 56-. Their
OC/TR-re-targeted cytolytic activity against Igrov-1 ovarian-
carcinoma cells was approximately as high in responders as in non-responders. Following most therapeutic cycles, the immunophenotype of lymphocytes recovered from the peritoneal fluid was similar to that of the infused T cells (i.e., mainly CD3+, 4-, 8+) and they 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
lymphopenia lasting for about 7 days, low (i.e., 5 to 13 ng/ml) serum concentrations 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
immunomodulation and anti-
tumor effects but virtually no systemic
immunomodulation.