Intraperitoneal administration of interferon-gamma to carcinoma patients enhances expression of tumor-associated glycoprotein-72 and carcinoembryonic antigen on malignant ascites cells.

Purpose: The study was designed to determine whether in vivo interferon gamma (IFN-gamma) 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-gamma (ie, 0.1 to 100 MU) intraperitoneally (IP) each week for 8 weeks.

CA 72-4 measurement of tumor-associated glycoprotein 72 (TAG-72) as a serum marker in the management of gastric carcinoma.

The presence of three distinct serum markers of carcinoma, tumor-associated glycoprotein 72 (TAG-72; as measured by the CA 72-4 assay), CA 19-9, and carcinoembryonic antigen (CEA), was evaluated in 194 patients diagnosed with either malignant (n = 94) or benign (n = 100) gastric disease. Of the 94 patients diagnosed with gastric carcinoma, the percentage of patients whose serum samples were positive for TAG-72, CA 19-9, or CEA was 42.6, 31.

Tumor-associated glycoprotein-72 serum levels complement carcinoembryonic antigen levels in monitoring patients with gastrointestinal carcinoma. A longitudinal study.

Eighty-two patients diagnosed with gastrointestinal (GI) adenocarcinoma were evaluated before and for 26 months after primary tumor resection for the presence of two serum tumor markers: tumor-associated glycoprotein-72 (TAG-72) and carcinoembryonic antigen (CEA). Elevated TAG-72 and CEA serum levels were found preoperatively in 32 (39%) and 34 (41.5%) of the 82 patients, respectively.

Evidence for the elevation of serum carcinoembryonic antigen and tumor-associated glycoprotein-72 levels in patients administered interferons.

Sera were collected from 111 patients diagnosed with adenocarcinoma or nonadenocarcinoma malignancies who received different schedules of interferon (IFN)-gamma or IFN-beta ser alone or in combination. Serum carcinoembryonic antigen (CEA) and tumor-associated glycoprotein-72 (TAG-72) antigen levels were measured to determine whether interferon could enhance the tumor shedding and, thereby, the serum level of either tumor antigen. Less than 10% of the sera samples from patients diagnosed with nonadenocarcinoma malignancies (e.

Clinical evaluation of the new tumor marker TAG-72.

Tumor-associated glycoprotein-72 (TAG-72) is a high molecular weight glycoprotein found in the sera of patients diagnosed with gastrointestinal and other malignancies. TAG-72 was detected in the serum of a significant percentage of patients whose CEA levels were negative which underscores the possibility of exploiting the complementarity of the two tumor markers in the diagnosis of gastrointestinal (G.I.

Carcinoembryonic antigen regulation in human colorectal tumor cells by a site-selective cyclic AMP analogue: a comparison with interferon-gamma.

Treatment of human colorectal tumor cells (LS174T, HT-29, and WiDr) with analogues of cyclic AMP (cAMP) (dibutyryl-cAMP and 8-Cl-cAMP) selectively enhances the expression of carcinoembryonic antigen (CEA). Dose and temporal kinetics results revealed that 8-Cl-cAMP was approximately 100-fold more potent than dibutyryl-cAMP for increasing CEA expression. Results demonstrated that 8-Cl-cAMP treatment of LS174T quantitatively increased CEA levels in cell extracts 2-fold, increased anti-CEA monoclonal antibody (MAb) binding to the tumor cell surface, and induced the appearance of CEA-related mRNA transcripts.

Maintenance of expression of tumor antigens in three-dimensional in vitro human tumor gel-supported histoculture.

Tumor-specific antigens are important in the study of tumor biology, tumor diagnosis and prognosis and possibly in tumor therapy. We demonstrate in this report that surgical specimens of colon, breast and ovarian tumors in native-state in vitro gel-supported three-dimensional in vitro histoculture maintain in vivo-like expression of the important tumor antigens TAG-72 and CEA. These results are in contrast to previously-reported studies indicating lack of expression of TAG-72 in monolayer cultures.

Regulation of human tumor antigen expression by biological response modifiers (BRMs).

The ongoing development of monoclonal antibody technology may eventually lead to the selective targeting of human carcinoma lesions of MoAbs conjugated with a variety of cytotoxic agents (i.e. radionuclides, drugs, etc.

Applications of monoclonal antibodies and recombinant cytokines for the treatment of human colorectal and other carcinomas.

Monoclonal antibodies (MAbs) which recognize a human tumor antigen, termed tumor-associated glycoprotein-72 (TAG-72), have successfully been used to localize primary as well as metastatic colorectal tumor lesions in patients. The localization of the anti-TAG-72 MAbs has also been exploited intraoperatively using a hand-held gamma probe. That procedure, termed radioimmunoguided surgery (RIGS), has identified occult tumors which were not detected using standard external imaging techniques.

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.

Clinical evaluation of serum tumor-associated glycoprotein-72 as a novel tumor marker for colorectal cancer patients.

A novel tumor marker, tumor-associated glycoprotein-72 (TAG-72), has been identified using monoclonal antibody (MAb) B72.3. Using immunohistochemical techniques, TAG-72 has been found in carcinomas of various origin including colon, stomach, breast, lung, prostate, and ovary, as well as in body fluids.

New concepts in monoclonal antibody based radioimmunodiagnosis and radioimmunotherapy of carcinoma.

It is now generally agreed that while numerous monoclonal antibodies (MAbs) have been shown to efficiently target tumors in patients, much still needs to be accomplished to optimize MAb based tumor targeting and the use of MAbs in the therapy of human carcinoma. This article will review some recent studies undertaken in our laboratory in an attempt to generate novel recombinant constructs and test new principles to aid in optimizing MAb based diagnosis and therapy. Three areas will be covered: (a) the analysis of dose fractionation protocols; (b) the generation of recombinant/chimeric (rec/chi) MAbs including the generation of a single chain antigen binding protein (SCA); and (c) the use of recombinant interferons (rec IFNs) to selectively up-regulate tumor antigen expression.

Monoclonal antibodies in the management of carcinoma patients.

The use of monoclonal antibodies (MAbs) in the clinical management of carcinoma patients is reported in the present review. Among the various MAbs generated, MAb B72.3 (LTIB, National Cancer Institute, U.

Regulation of carcinoembryonic antigen expression in different human colorectal tumor cells by interferon-gamma.

The regulation of carcinoembryonic antigen (CEA) expression by recombinant human interferon-gamma (IFN-gamma) was studied in a series of 7 human colorectal tumor cell lines at various stages of differentiation. Two of the colorectal cell lines were poorly differentiated and did not constitutively express CEA. IFN-gamma treatment, however, induced CEA expression in one of those lines (i.

CA 72-4 radioimmunoassay in the diagnosis of malignant effusions. Comparison of various tumor markers.

We evaluated the utility of the CA 72-4, CEA, CA 125, CA 19-9 and CA 15-3 radioimmunoassays for the detection of tumor-associated antigens (TAAs) in effusions of malignant vs. benign origin. Fluids were obtained from 51 patients with adenocarcinomas, 27 with non-epithelial malignancies, and 68 with benign disorders.

Augmentation of tumor antigen expression by recombinant human interferons: enhanced targeting of monoclonal antibodies to carcinomas.

The use of Mabs for the detection and treatment of human carcinoma lesions can still be regarded in its infancy. As with other new approaches to cancer therapy, several conceptual as well as real problems exist when designing clinical protocols for Mab-directed immunotherapy. From the Mab standpoint, studies using the intact IgG have shown that, in a majority of patients injected with IgG, human anti-mouse IgG antibodies develop that hamper the effectiveness of subsequent antibody administration.

Serologic mapping and biochemical characterization of the carcinoembryonic antigen epitopes using fourteen distinct monoclonal antibodies.

A series of 14 monoclonal anti-carcinoembryonic antigen (CEA, Mr 180,000) antibodies (MAbs) that show a strong degree of selective reactivity for human colon carcinomas versus normal adult tissues were used to construct a serological map of the CEA molecule. The MAbs were generated using extracts of colon carcinomas as immunogen and are thus given a COL designation. None of the 14 COL-MAbs tested were reactive with purified non-specific cross-reacting antigen (NCA, Mr 55,000) from normal lung, although some showed reactivity to human granulocytes.

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.

Parameters involved in the enhancement of monoclonal antibody targeting in vivo with recombinant interferon.

The effects of recombinant human leukocyte (clone A) interferon (rHu-IFN-alpha A) were investigated on the expression of monoclonal antibody (MAb)-defined tumor antigens expressed on human mammary and colon carcinomas. The rHu-IFN-alpha A treatment substantially increased the localization of radiolabeled MAb B6.2-F(ab')2 to the transplantable Clouser human mammary carcinoma, as well as to the moderately differentiated human colon xenograft WiDr, when grown as s.

Recombinant interferon enhances monoclonal antibody-targeting of carcinoma lesions in vivo.

Heterogeneity in the expression of tumor-associated antigens, as defined by the binding of monoclonal antibodies, is a characteristic common to most, if not all, human carcinoma cell populations. Antigen-negative cells within the population can escape detection and therapy by their failure to bind the appropriate antibody. Therefore, the extent of antigenic heterogeneity is an important consideration when designing protocols for the management of cancer by administration of monoclonal antibodies.

Influence of interferon on the functional expression of natural killer target structures of murine lymphoma cells.

Murine lymphoma cells (YAC-1), induced by Moloney leukemia virus, nontreated (YAC) or pretreated in vitro with interferon (YAC-IF), were tested for their susceptibility to natural killer (NK)-mediated cytolysis. In line with previous reports YAC-IF were less susceptible to NK lysis than YAC cells. In cold competition assay, YAC-IF inhibited cytotoxicity to a lesser extent than YAC lymphoma when labeled target YAC cells were used.

Increased immunogenicity of murine lymphoma cells following exposure to gamma rays in vivo.

Studies performed in our laboratory showed that a marked increase in immunogenicity occurred in murine lymphoma cells exposed to a mutagenic compound such as 5 (3,3'-dimethyl-1-triazeno)-imidazole-4-carboxamide (DTIC in vivo or in vitro. Subsequently, further experiments were conducted to test whether ionizing radiations would be able to affect the immunogenic properties of cancer cells in a mouse leukemia model. Male CD2F1 mice were inoculated with histocompatible L1210 Ha leukemia and treated with 400 R of total-body irradiation.