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

John W. Greiner, Fiorella Guadagni, David Goldstein, Richard V. Smalley, Ernest C. Borden, Jean F. Simpson, Alfredo Molinolo, Jeffrey Schlom

Research output: Contribution to journalArticlepeer-review

Abstract

Purpose: The study was designed to determine whether in vivo Interferon gamma (IFN-γ) 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-γ (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-γ 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-γ 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-γ in all seven patients, as evidenced by the enhanced binding of anti-TAG-72 MoAbs to the tumor-cell surface. In some cases, IFN-γ 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, ascltes-derived tumor cells from two patients with gastrointestinal carcinoma also expressed enhanced CEA levels after IFN-γ. The increased TAG-72 and CEA expression were observed at low IFN-γ doses (ie, 0.1 to 1.0 MU), which were well tolerated by all patients. Conclusions: The ability of IFN-γ 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.

Original languageEnglish
Pages (from-to)735-746
Number of pages12
JournalJournal of Clinical Oncology
Volume10
Issue number5
Publication statusPublished - 1992

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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