Selective interferon-induced enhancement of tumor-associated antigens on a spectrum of freshly isolated human adenocarcinoma cells.
Freshly isolated cells from patients with pleural or peritoneal effusions cytologically diagnosed as adenocarcinoma (n = 43), malignant nonepithelial neoplasms (n = 10), and benign (n = 8) were analyzed for expression of constitutive levels of the tumor antigens TAG-72 [recognized by monoclonal antibody (MAb) B72.3] and carcinoembryonic antigen (CEA) (recognized by MAb COL-4) as well as the class I and class II major histocompatibility (MHC) antigens, and the ability of human interferons (Hu-IFNs) to enhance cell surface expression of those antigens as measured by MAb binding. Both type I and type II IFNs enhanced the expression of TAG-72 and CEA and altered the level of expression of the MHC antigens. Comparative studies of three different Hu-IFNs (IFN-alpha A, IFN-beta ser, and IFN-gamma) revealed that IFN-gamma was the most potent in augmenting either B72.3 or COL-4 binding. Unlike the IFN-gamma -mediated induction of the class II human leukocyte antigens, the change in tumor antigen expression consisted of enhanced constitutive antigen expression; de novo induction of either TAG-72 or CEA could not be achieved by either type I or type II IFN. Of 43 effusions isolated from different adenocarcinoma patients, 42 (97.7%) expressed either CEA or TAG-72, and treatment with Hu-IFN increased the level of expression of either antigen in 36 of 42 samples (85.7%). These studies demonstrate the augmentation of tumor-associated antigens on human carcinoma cells isolated from serous effusions by Hu-IFNs which may be used to enhance the targeting of conjugated MAbs to human carcinoma lesions.
Guadagni
F
F
Laboratory of Tumor Immunology and Biology, National Cancer Institute, Bethesda, MD 20892.
Schlom
J
J
Johnston
W W
WW
Szpak
C A
CA
Goldstein
D
D
Smalley
R
R
Simpson
J F
JF
Borden
E C
EC
Pestka
S
S
Greiner
J W
JW
D000230:Adenocarcinoma / Q000276:immunology*; D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm / Q000096:biosynthesis*; D000954:Antigens, Surface / Q000096:biosynthesis*; D002272:Carcinoembryonic Antigen / Q000096:biosynthesis; D005122:Exudates and Transudates / Q000166:cytology / Q000276:immunology; D006023:Glycoproteins / Q000096:biosynthesis; D006801:Humans; D007370:Interferon Type I / Q000494:pharmacology; D000068556:Interferon beta-1a; D000068576:Interferon beta-1b; D016899:Interferon-beta; D007371:Interferon-gamma / Q000494:pharmacology; D007372:Interferons / Q000494:pharmacology*; D011863:Radioimmunoassay; D011994:Recombinant Proteins / Q000494:pharmacology
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; D000068576:Interferon beta-1b; D016899:Interferon-beta; D007371:Interferon-gamma; D007372:Interferons; D000068556:Interferon beta-1a