In vitro and in vivo regulation of tumor antigen expression by human recombinant interferons.
In vitro treatment with either type I or type II interferon (IFN) can selectively enhance the expression of several tumor antigens, such as the carcinoembryonic antigen (CEA) and the tumor-associated glycoprotein-72 (TAG-72) in different human carcinoma cell lines and result in enhanced level of monoclonal antibody (MAb) binding to the cell surface. In vivo animal studies demonstrated that treatment of athymic mice with a type I interferon [i.e. interferon-alpha (A)] significantly increased the expression of a 90 kDa tumor antigen which improved the targeting of a MAb to the carcinoma xenograft. More recent studies reported that in vitro IFN treatment of human adenocarcinoma cells isolated from human malignant serous effusions selectively increased the expression of TAG-72 and CEA. One can envision that the ability of these cytokines to upregulate the level of expression of human tumor antigens presents an important experimental model in which to study the regulation of markers often correlated with epithelial cell differentiation. In addition, the increase of selective MAb-defined antigens may also be exploited in an adjuvant setting to localize higher amounts of MAbs to the tumor cell surface and, thereby, improve the effectiveness of a MAb for tumor diagnosis and, possibly, therapy.
Guadagni
F
F
Laboratory of Tumor Immunology and Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892.
Schlom
J
J
Greiner
J W
JW
D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism; D000951:Antigens, Neoplasm / Q000096:biosynthesis*; D000954:Antigens, Surface / Q000096:biosynthesis; D001666:Binding Sites, Antibody; D002272:Carcinoembryonic Antigen / Q000096:biosynthesis*; D006023:Glycoproteins / Q000096:biosynthesis*; D006801:Humans; D007370:Interferon Type I / Q000494:pharmacology*; D007371:Interferon-gamma / Q000494:pharmacology*; D051379:Mice; D008819:Mice, Nude; D011994:Recombinant Proteins; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D000954:Antigens, Surface; D002272:Carcinoembryonic Antigen; D006023:Glycoproteins; D007370:Interferon Type I; D011994:Recombinant Proteins; C047052:tumor-associated antigen 72; D007371:Interferon-gamma