Modulation of tumor-associated antigen expression on human pancreatic and prostate carcinoma cells in vitro by alpha- and gamma-interferons.
Interferons (IFNs) are known to have antiviral effects and have been shown to enhance the expression of tumor-associated antigens (TAA) on different target cells. In our current study, we investigated the potential of IFN-alpha or IFN-gamma to enhance the expression of the TAAs recognized by monoclonal antibodies (MAbs) 19-9, B72.3, 17-1A, and BR55-2 on pancreatic cancer cell lines and the potential of IFN-gamma to modulate the expression of a single TAA, BR55-2, on nonpancreatic cancer cell lines. Expression of these TAAs, percentage of positive cells and mean fluorescence intensity, was measured by flow cytometry. In these studies, we provide evidence that one prostate (DU 145) and two pancreatic (HPAF and BxPC-3) cancer cell lines that moderately express BR55-2 can be upregulated by IFN-gamma treatment, with optimal enhancement occurring between 48 and 72 h with 1,000 IU/ml. Cell lines that highly expressed BR55-2 could not be further upregulated by the doses of IFNs tested during the various periods used. IFN-alpha or IFN-gamma treatments did not significantly change the levels of TAA expression on pancreatic cancer cell lines that bound MAbs 17-1A or 19-9. Cell lines that did not bind MAbs 17-1A, 19-9, B72.3, or BR55-2 before IFN treatments could not be induced to express these antigens after treatment. Although antigen expression does not ensure detectable therapeutic benefit, increased antigen expression on tumor tissues may augment the efficacy of MAbs bearing radionuclides, toxins, or effector cells to the tumor site. In each of these situations, the use of IFNs to enhance TAA expression, particularly IFN-gamma, may merit consideration.
Sivinski
C L
CL
Veterans Administration Medical Center, Omaha, Nebraska, USA.
Lindner
D J
DJ
Borden
E C
EC
Tempero
M A
MA
D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm / Q000378:metabolism*; D015295:Antigens, Tumor-Associated, Carbohydrate / Q000378:metabolism; D018395:CA-19-9 Antigen / Q000378:metabolism; D006017:Glycolipids / Q000276:immunology / Q000378:metabolism; D006023:Glycoproteins / Q000378:metabolism; D006801:Humans; D007370:Interferon Type I / Q000494:pharmacology*; D007371:Interferon-gamma / Q000494:pharmacology*; D008297:Male; D010190:Pancreatic Neoplasms / Q000276:immunology* / Q000628:therapy*; D011471:Prostatic Neoplasms / Q000276:immunology* / Q000628:therapy*; D011994:Recombinant Proteins; D014407:Tumor Cells, Cultured; D015854:Up-Regulation
D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D015295:Antigens, Tumor-Associated, Carbohydrate; D018395:CA-19-9 Antigen; D006017:Glycolipids; D006023:Glycoproteins; D007370:Interferon Type I; D011994:Recombinant Proteins; C050928:carcinoma-associated antigen 17-1A; C047052:tumor-associated antigen 72; D007371:Interferon-gamma