Journal of Clinical Oncology, Vol 14, 2031-2042, Copyright © 1996 by American Society of Clinical Oncology
Systemic administration of recombinant interferon alfa in carcinoma patients upregulates the expression of the carcinoma-associated antigens tumor-associated glycoprotein-72 and carcinoembryonic antigen
M Roselli, F Guadagni, O Buonomo, A Belardi, V Vittorini, R Mariani-Costantini, JW Greiner, CU Casciani and J Schlom
Department of Surgery, University of Rome Tor Vergata, Italy.
PURPOSE: The ability of interferons (IFNs) to enhance tumor-associated
antigen expression may be an important approach to enhance the efficacy of
some monoclonal antibody (MAb)-based protocols for tumor diagnosis and/or
therapy. The present study was designed to determine whether systemic IFN
alpha-2a administration (via the intramuscular [IM] route) could upregulate
the expression of tumor-associated glycoprotein-72 (TAG-72) and/or
carcinoembryonic antigen (CEA) at histologically confirmed sites of
carcinoma. PATIENTS AND METHODS: Eighteen patients diagnosed with
gastrointestinal (GI) carcinoma received systemic IFN alpha-2a according to
four dose schedules. In cohorts I and II, patients received two injections
of 3 or 6 x 10(6) U IFN alpha-2a per injection, respectively. Patients in
cohorts III and IV received the same doses of IFN alpha-2a, 3 and 6 x 10(6)
U, respectively, but three injections were given. Tumor and normal colonic
mucosa biopsies were obtained from each patient by endoscopy before IFN
alpha-2a and after IFN alpha-2a at surgery. The levels of TAG-72 and CEA
expression were measured by (1) immunohistochemistry and reported as
percent antigen- positive tumor cells, as well as the relative staining
intensity, and (2) a quantitative radioimmunoassay. RESULTS: TAG-72 and CEA
levels were consistently increased in tumor biopsies taken from patients in
cohorts III and IV. For example, of 10 patients treated in cohorts III and
IV, eight had enhanced TAG-72 expression when measured either as percentage
TAG-72-positive tumor cells or as an increased MAb staining intensity
following IFN alpha-2a. CEA expression in tumor biopsies from seven of 10
patients in cohorts III and IV was also elevated following IFN alpha-2a
treatment. Quantitative analysis of TAG-72 and CEA levels in tumor biopsies
confirmed higher tumor antigen levels following IFN alpha-2a
administration. No such increases in TAG-72 or CEA levels were observed in
tumor samples taken from patients in cohorts I and II. CEA or TAG-72
expression in samples of histologically confirmed normal colonic mucosa
showed little or no change after IFN alpha-2a treatment. CONCLUSION:
Systemic IFN alpha-2a administration can upregulate TAG-72 and CEA
expression at distal tumor sites, which may play an important role in
immunodiagnosis and therapy.
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