Despite encouraging responses to treatment, 70% to 80% of women with
ovarian cancer will recur due to subclinical residual disease. One experimental agent that merits testing in this setting is the immunocytokine
huKS-IL2. Immunocytokines are fusion
proteins consisting of a humanized
monoclonal antibody linked to
IL-2 (or other
cytokines). The humanized
monoclonal antibody (mAb) huKS, which recognizes the
epithelial cell adhesion molecule (
EpCAM), has been used to construct the immunocytokine
huKS-IL2. To determine the potential
therapeutic use of
huKS-IL2 in
ovarian cancer, the authors evaluated the expression of
EpCAM in these
cancers and investigated the effects of
huKS-IL2 on peritoneal white blood cells and peripheral blood mononuclear cells from women with
ovarian cancer.
EpCAM expression was determined by immunohistochemistry using both
huKS-IL2 and the parent KS1/4 antibody.
Ascites fluid was collected and the cellular fraction cultured with or without
huKS-IL2 to evaluate the cellular content and potential anti-
tumor effects of the peritoneal effector cells (PECs). Peritoneal cells were incubated with
FITC-conjugated KS antibody to determine the relative amount of
EpCAM-positive cells. Nonadherent cells were analyzed by flow cytometry for hematopoietic origin with CD45 mAb and for CD69 expression as an indication of immune cell activation.
EpCAM-positive NIH:OVCAR-3 cells were radiolabeled as targets in a
chromium release assay with either PECs or PBMCs as effector cells in the presence or absence of 0.25 mcg/mL
huKS-IL2. Differences between treatments were determined by t test. Thirty-two of thirty-three (97%)
ovarian cancers were found to express
EpCAM via immunohistochemistry. Eleven cases were stained using both KS1/4 and
huKS-IL2, and identical patterns of staining were seen. All
ascites samples tested had
EpCAM-positive cells by flow cytometry. The mean fluorescence intensity of CD69 expression on peritoneal WBCs was increased from 20.7 to 43.9 as a result of culturing with
huKS-IL2, indicating effector cell activation. In
chromium release assays, KS-IL2 facilitated cell lysis of NIH:OVCAR-3 by PBMCs from both healthy controls and patients with
ovarian cancer. PECs from all cases tested showed significant cell lysis induced by
huKS-IL2 compared with untreated control cultures. Based on these findings,
huKS-IL2 warrants further investigation as a potential
immunotherapy for patients with
epithelial ovarian cancer, preferably in a minimal disease setting as seen after complete
cytoreductive surgery, after a complete clinical response to primary
therapy, or when elevated CA-125 levels predict recurrent disease prior to clinical relapse.