Detection of human ovarian tumor-associated antigens by antibodies isolated from ovarian carcinoma ascitic fluid

Rao, G. Sasibhushana; Hanjani, Parviz

doi:10.1016/0002-9378(88)90500-5

Cited by 7 publications

(5 citation statements)

References 15 publications

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“…The antibody levels increase as the disease progresses (Taylor and Gercel-Taylor, 1998). Furthermore, ascitic immunoglobulins of IgM and IgG classes have been described (Silburn et al, 1984a, b;Rao and Hanjani, 1988). They are present either as circulating free antibodies, in immune complexes, or bound to tumour cells and cellular fragments (Silburn et al, 1983;Runowicz et al, 1989;Kawata and Sekiya, 1998;Taylor and Gercel-Taylor, 1998).…”

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confidence: 99%

Ascitic complement system in ovarian cancer

et al. 2005

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Ovarian cancer spreads intraperitoneally and forms fluid, whereby the diagnosis and therapy often become delayed. As the complement (C) system may provide a cytotoxic effector arm for both immunological surveillance and mAb-therapy, we have characterised the C system in the intraperitoneal ascitic fluid (AF) from ovarian cancer patients. Most of the AF samples showed alternative and classical pathway haemolytic activity. The levels of C3 and C4 were similar to or in the lower normal range when compared to values in normal sera, respectively. However, elevated levels of C3a and soluble C5b-9 suggested C activation in vivo. Malignant cells isolated from the AF samples had surface deposits of C1q and C3 activation products, but not of C5b-9 (the membrane attack complex; MAC). Activation could have become initiated by anti-tumour cell antibodies that were detected in the AFs and/or by changes on tumour cell surfaces. The lack of MAC was probably due to the expression of C membrane regulators CD46, CD55 and CD59 on the tumour cells. Soluble forms of C1 inhibitor, CD59 and CD46, and the alternative pathway inhibitors factor H and FHL-1 were present in the AF at concentrations higher than in serum samples. Despite the presence of soluble C inhibitors it was possible to use AF as a C source in antibody-initiated killing of ovarian carcinoma cells. These results demonstrate that although the ovarian ascitic C system fails as an effective immunological surveillance mechanism, it could be utilised as an effector mechanism in therapy with intraperitoneally administrated mAbs, especially if the intrinsic C regulators are neutralised.

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confidence: 99%

Ascitic complement system in ovarian cancer

et al. 2005

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“…Immunoglobulins which were liberated from ascitic ICs by dissociating reagents were shown to react with ovarian cancer tissues by immunohistological staining [9][10][11][12]15]. We also attempted to purify individual constituents from ascitic ICs in a similar way, but found that this approach had several inherent technical limitations for further evaluation, including only partial dissociation with accompanying denaturation and low titers of the resulting heterogeneous antibodies.…”

Section: Discussionmentioning

confidence: 99%

“…The availability of large amounts of ICs from ascites, compared with those from the patient's serum, has facilitated their characterization [7][8][9][10][11][12][13][14][15]. Although individual nonantigenic constituents bound within the ascitic ICs have been characterized, the origin and nature of antigenic components remain to be identified, mainly due to technical problems and the lack of suitable probes [16].…”

Section: Introductionmentioning

confidence: 99%

Detection of Epithelial Ovarian-Cancer-Associated Antigens Involved in Immune Complexes by Monoclonal Antibodies

Kawata

Sekiya²

1998

Tumor Biol

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To detect antigenic molecules involved in immune complexes (ICs) in patients with epithelial ovarian cancer, we developed several monoclonal antibodies (Mabs) by hybridoma technology from mice immunized with ovarian cancer tissues. Hybridoma supernatants were differentially screened with a panel of ICs purified from ascites of patients with ovarian cancer and with ICs from pooled normal human sera by the enzyme-linked immunosorbent assay (ELISA). From about 6,000 supernatants screened in 6 fusions, 4 Mabs showing preferential binding to the ascitic ICs were selected. Their antibody specificity was further examined with serum-free conditioned media of various cancer cell lines by an ELISA inhibition assay. The reactivity of 3 Mabs was inhibited by the media of epithelial ovarian cancer cell lines, but not by any of the nonovarian cell lines tested, suggesting that the target antigens were derived from ovarian cancer cells. Furthermore, ICs detected by one Mab, designated 2F11, were elevated in the sera from 18 of 42 (42.9%) patients with epithelial ovarian cancer, but not in those from 39 patients with benign ovarian tumors or from 29 healthy individuals (with the exception of 1 serum), using sandwich ELISA with protein A as the capture reagent.

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“…Therefore, new diagnostic strategies such as immunoscintigraphic approaches using tumor-associated antigen (TAA)-specific, radiolabelled monoclonal antibodies (mAb) for tumor targeting, e.g., REGAJ (resection guided by antibodies) and RIGS (radioimmunoguided surgery), attempted intraoperatively to trace micrometastasis [4][5][6][7][8]. Although initial studies showed promising results, surveys of mAb-distribution in vivo demonstrated radioactive accumulation in ascites and benign tissue as well as in tumor tissue [7,9,10]. Jäger et al [7] showed that although 131 I-OC125-F(ab´) 2 localized to ovarian cancer micrometastasis in vivo, radiolabelled mAb also was taken up by not tumor-infiltrated tissue.…”

Section: Introductionmentioning

confidence: 99%

“…Jäger et al [7] showed that although 131 I-OC125-F(ab´) 2 localized to ovarian cancer micrometastasis in vivo, radiolabelled mAb also was taken up by not tumor-infiltrated tissue. Other investigators detected high amounts of radioactivity in the peritoneal cavity and in ascites fluid of ovarian cancer patients after immunoscintigraphy [9,10]. Whether 131 I-OC125-F(ab´) 2 targeting was due to its specific binding to CA-125 (cancer antigen) or merely to nonspecific uptake was not clear.…”

Section: Introductionmentioning

confidence: 99%

Distribution of radiolabelled anti‐CA125 monoclonal antibody OC125‐F(ab′)2‐fragment following resection guided by antibodies (REGAJ) in ovarian cancer patients

Uttenreuther-Fischer¹,

Feistel²,

Wolf³

et al. 1997

J. Clin. Lab. Anal.

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Ovarian cancer is a highly malignant tumor of mainly postmenopausal women. The long-term prognosis of this malignancy is largely determined by micrometastasis present at the time of second-look surgery. In general, patients face a poor outcome. New radio-immunoscintigraphic methods to target tumor tissue specifically via antigen-antibody binding were developed. However, few studies so far investigated the pattern of in vivo distribution of radiolabelled mAbs and/ or the specificity of antigen-antibody interaction. In this study we examined the immunological interaction and distribution of 131l-OC125-F(ab')2-fragment, an anti-CA-125 mAb, in patients with CA-125 positive ovarian malignancies. Sixteen patients with primarily CA-125 positive gynecological tumors underwent REGAJ surgery. Biopsies of tumor tissue and not tumor infiltrated tissue, serum, and ascites were sampled during or prior to REGAJ surgery, respectively. After preparation of tissue cytosols, samples were assessed for CA-125 and radioactive uptake. By radiochromatography immunological analysis for presence of the target antigen CA-125, the mAb 131l-OC125-F(ab')2-fragment, and immune complexes was performed on different specimen. CA-125 concentrations were higher in serum samples, ascites, and malignant tissue biopsies of malignoma patients compared to those without signs of malignant disease. CA-125 was higher in the tissue cytosol than in the cell membrane fraction. Gel filtration revealed CA-125 with moieties of 75,000 to > 600,000 d. Accumulation of radioactivity was more frequently associated with the presence of unbound 131l-OC125-F(ab')2-fragment or high molecular weight immune complexes. Radioactive uptake, however, was not confined to tissue of high CA-125 expression. Moreover, both immune complex as well as 131l-OC125-F(ab')2-fragment could be isolated from cytosols of tissue not infiltrated by tumor cells as well. Our study demonstrates that the majority of CA-125 is located intracellularly and thus inaccessible to 131l-OC125-F(ab')2-fragment per se. The uptake of 131l-OC125-F(ab')2-fragment into the cytosol of tumor-free and malignant tissue samples prompts us to speculate that certain mechanisms for antigen-specific and nonspecific cellular trafficking of mAbs do exist. We present a model to explain our observations.

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Detection of human ovarian tumor-associated antigens by antibodies isolated from ovarian carcinoma ascitic fluid

Cited by 7 publications

References 15 publications

Ascitic complement system in ovarian cancer

Ascitic complement system in ovarian cancer

Detection of Epithelial Ovarian-Cancer-Associated Antigens Involved in Immune Complexes by Monoclonal Antibodies

Distribution of radiolabelled anti‐CA125 monoclonal antibody OC125‐F(ab′)2‐fragment following resection guided by antibodies (REGAJ) in ovarian cancer patients

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