Journal of Clinical Oncology, Vol 10, 735-746, Copyright © 1992 by American Society of Clinical Oncology

ARTICLES

Intraperitoneal administration of interferon-gamma to carcinoma patients enhances expression of tumor-associated glycoprotein-72 and carcinoembryonic antigen on malignant ascites cells

JW Greiner, F Guadagni, D Goldstein, RV Smalley, EC Borden, JF Simpson, A Molinolo and J Schlom
Laboratory of Tumor Immunology and Biology, National Cancer Institute/National Institutes of Health, Bethesda, MD 20892.

PURPOSE: The study was designed to determine whether in vivo interferon gamma (IFN-gamma) administration could enhance tumor antigen expression on the surface of human tumor cells. MATERIALS AND METHODS: Eight patients (six with ovarian and two with gastrointestinal tumors) with a diagnosis of adenocarcinoma with secondary malignant ascites were given weekly escalating doses of IFN-gamma (ie, 0.1 to 100 MU) intraperitoneally (IP) each week for 8 weeks. Tumor cells were isolated from the patients' ascites samples, which were collected three times per week: before and 24 and 48 hours post-IFN-gamma administration. The level of expression of tumor-associated glycoprotein-72 (TAG-72) and carcinoembryonic antigen (CEA) was measured using flow cytometry and immunocytochemistry. RESULTS: IFN-gamma administered IP dramatically increased TAG-72 (as measured by binding of anti-TAG-72 monoclonal antibodies [MoAbs] B72.3 and CC 49) and CEA (measured by MoAb COL-1) expression on the surface of the carcinoma cells. The ascites-derived tumor cells from seven of the eight patients constitutively expressed TAG-72, and the level of TAG-72 expression was increased by IFN-gamma in all seven patients, as evidenced by the enhanced binding of anti-TAG- 72 MoAbs to the tumor-cell surface. In some cases, IFN-gamma treatment increased the percentage of MoAb B72.3-reactive tumor cells from 10% to greater than 90%, and those changes were further corroborated by similar increases in the MoAb staining intensity observed with immunoperoxidase analysis. In addition, ascites-derived tumor cells from two patients with gastrointestinal carcinoma also expressed enhanced CEA levels after IFN-gamma. The increased TAG-72 and CEA expression were observed at low IFN-gamma doses (ie, 0.1 to 1.0 MU), which were well tolerated by all patients. CONCLUSIONS: The ability of IFN-gamma given IP to increase TAG-72 and CEA expression on tumor cells in vivo provides additional argument for the use of the cytokine as an adjuvant to enhance MoAb binding to human carcinoma-cell populations.

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