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

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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

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Carcinoembryonic Antigen
Ascites
Interferon-gamma
Carcinoma
Neoplasms
Monoclonal Antibodies
tumor-associated antigen 72
Neoplasm Antigens
Flow Cytometry
Adenocarcinoma
Immunohistochemistry
Staining and Labeling
Cytokines

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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Intraperitoneal administration of interferon-gamma to carcinoma patients enhances expression of tumor-associated glycoprotein-72 and carcinoembryonic antigen on malignant ascites cells. / Greiner, John W.; Guadagni, Fiorella; Goldstein, David; Smalley, Richard V.; Borden, Ernest C.; Simpson, Jean F.; Molinolo, Alfredo; Schlom, Jeffrey.

In: Journal of Clinical Oncology, Vol. 10, No. 5, 1992, p. 735-746.

Research output: Contribution to journalArticle

Greiner, John W. ; Guadagni, Fiorella ; Goldstein, David ; Smalley, Richard V. ; Borden, Ernest C. ; Simpson, Jean F. ; Molinolo, Alfredo ; Schlom, Jeffrey. / Intraperitoneal administration of interferon-gamma to carcinoma patients enhances expression of tumor-associated glycoprotein-72 and carcinoembryonic antigen on malignant ascites cells. In: Journal of Clinical Oncology. 1992 ; Vol. 10, No. 5. pp. 735-746.
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title = "Intraperitoneal administration of interferon-gamma to carcinoma patients enhances expression of tumor-associated glycoprotein-72 and carcinoembryonic antigen on malignant ascites cells",
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.",
author = "Greiner, {John W.} and Fiorella Guadagni and David Goldstein and Smalley, {Richard V.} and Borden, {Ernest C.} and Simpson, {Jean F.} and Alfredo Molinolo and Jeffrey Schlom",
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T1 - Intraperitoneal administration of interferon-gamma to carcinoma patients enhances expression of tumor-associated glycoprotein-72 and carcinoembryonic antigen on malignant ascites cells

AU - Greiner, John W.

AU - Guadagni, Fiorella

AU - Goldstein, David

AU - Smalley, Richard V.

AU - Borden, Ernest C.

AU - Simpson, Jean F.

AU - Molinolo, Alfredo

AU - Schlom, Jeffrey

PY - 1992

Y1 - 1992

N2 - 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.

AB - 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.

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