title: Intraperitoneal administration of interferon-gamma to carcinoma patients enhances expression of tumor-associated glycoprotein-72 and carcinoembryonic antigen on malignant ascites cells.
abstract: OBJECTIVE
  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.
  
  
  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.
authors.affiliation: Laboratory of Tumor Immunology and Biology, National Cancer Institute/National Institutes of Health, Bethesda, MD 20892.
authors.forename: J W
authors.initials: JW
authors.lastname: Greiner
authors.forename: F
authors.initials: F
authors.lastname: Guadagni
authors.forename: D
authors.initials: D
authors.lastname: Goldstein
authors.forename: R V
authors.initials: RV
authors.lastname: Smalley
authors.forename: E C
authors.initials: EC
authors.lastname: Borden
authors.forename: J F
authors.initials: JF
authors.lastname: Simpson
authors.forename: A
authors.initials: A
authors.lastname: Molinolo
authors.forename: J
authors.initials: J
authors.lastname: Schlom
mesh_terms: D000951:Antigens, Neoplasm / Q000096:biosynthesis / Q000187:drug effects*; D001202:Ascitic Fluid / Q000276:immunology*; D002272:Carcinoembryonic Antigen / Q000096:biosynthesis / Q000187:drug effects*; D005260:Female; D005434:Flow Cytometry; D005770:Gastrointestinal Neoplasms / Q000276:immunology*; D006023:Glycoproteins / Q000096:biosynthesis / Q000187:drug effects*; D006801:Humans; D007263:Infusions, Parenteral; D007371:Interferon-gamma / Q000494:pharmacology*; D010051:Ovarian Neoplasms / Q000276:immunology*
chemical_list: D000951:Antigens, Neoplasm; D002272:Carcinoembryonic Antigen; D006023:Glycoproteins; C047052:tumor-associated antigen 72; D007371:Interferon-gamma