Detection of polymorphic epithelial mucins in the serum of systemic breast cancer patients using the monoclonal antibody, NCRC-11

Price, Michael R.; Clarke, Anthony J.; Robertson, J. F. R.; O'Sullivan, Colette; Baldwin, Robert; Blamey, R.W.

doi:10.1007/bf01740933

Cited by 20 publications

(6 citation statements)

References 19 publications

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“…2 a. Indirect immunoperoxidase staining of tissues using the GL-013 monoclonal antibody, a Intense, but heterogeneous staining of a specimen from a poorly differentiated gastric carcinoma, which is adjacent to unstained normal tissue and lymphoid cells towards the top of the figure, b Strong staining of goblet cells in normal colonic mucosae movements in marker levels [9,11,13,18]. The appearance of this mucin in the serum of cancer patients is considered to reflect disorganisation of tissue architecture in the breast as well as losses in the functional polarity in the malignant cell.…”

Section: Discussionmentioning

confidence: 99%

Reactivity of an anti-(human gastric carcinoma) monoclonal antibody with core-related peptides of gastrointestinal mucin

Price

Sekowski

Yang

et al. 1991

Cancer Immunol Immunother

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A murine anti-(human gastric carcinoma) monoclonal antibody, GL-013 (IgG1), which reacts with a high-molecular-mass glycoprotein from colorectal tumour tissue [Yang and Price (1989) Anticancer Res 9: 1707], was examined for reactivity against a panel of purified and partially purified antigens associated with tumours of the gastrointestinal tract. These included carcinoembryonic antigen (CEA), normal cross-reacting antigen, Y-hapten glycoproteins, and perchloric acid extracts and glycolipid preparations from colorectal tumours. While the GL-013 antibody failed to bind to these antigens, it was found to react strongly with synthetic peptides with sequences based upon that reported for the protein core of a human gastrointestinal mucin [Barnd et al. (1989) Proc Natl Acad Sci USA 86: 7159; Gum et al. (1989) J Biol Chem 264: 6480]. In control tests, a series of other anti-(colorectal tumour) antibodies (IgG1 and IgG3), with broad reactivity towards gastrointestinal carcinomas, as well as an anti-CEA antibody, (IgG1) failed to react with the synthetic peptides. It is concluded that the anti-(gastric carcinoma) monoclonal antibody GL-013 binds to a threonine-rich peptide epitope expressed within the protein core of gastrointestinal mucins.

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Section: Discussionmentioning

confidence: 99%

Reactivity of an anti-(human gastric carcinoma) monoclonal antibody with core-related peptides of gastrointestinal mucin

Price

Sekowski

Yang

et al. 1991

Cancer Immunol Immunother

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“…SialyI-Tn-KLH was provided as a sterile, pyrogen-free pharmaceutically acceptable formulation by Biomira Inc. Detox (RIBI ImmunoChem Research Inc., Hamilton, Mont., USA) is a sterile, pyrogen-free preparation [19] and is formulated as a lyophilized oil droplet emulsion containing monophosphoryl lipid A and cell wall skeleton from Mycobacterium phlei. Immediately prior to injection, the STn-KLH was reconstituted with phosphate-buffered saline (PBS) and added to the lyophilized Detox to give a final volume of approximately 1.0 ml at a final concentration of STn-KLH of 25, 100 or 500 gg.…”

Section: Antigens and Haptens All Haptens And Immunoconjugates Were mentioning

confidence: 99%

“…As human breast carcinoma cells may be deficient in a key galactosyltransferase [23], Tn is exposed and premature sialation of Tn can occur leading to the formation of sialyl-Tn [7,8,10] (STn = DAcNeu~2-6o~GalNAc-O-Ser/Thr). All three epitopes, Tn, TF and STn, are strongly expressed on human carcinoma cells [7,8,21] and may be associated with cancer progression and metastasis of human carcinomas [11,13,19,21].…”

Section: Introductionmentioning

confidence: 99%

Immunization of breast cancer patients using a synthetic sialyl-Tn glycoconjugate plus Detox adjuvant

MacLean

Reddish²,

Koganty³

et al. 1993

Cancer Immunol Immunother

176

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We have synthesized various formulations that have potential for active specific immunotherapy (ASI) of human cancers. Sialyl-Tn (STn) is a potentially important target structure for ASI because its expression on mucins is a strong, independent predictor of poor prognosis, suggesting that it may have functional significance in the metastatic process. In this first pilot study of synthetic sialyl-Tn hapten conjugated to keyhole limpet hemocyanin (STn-KLH), with Detox adjuvant, toxicity and humoral immunogenicity were assessed in 12 patients with metastatic breast cancer. Toxicity was minimal, restricted to local cutaneous reactions (apart from transient nausea and vomiting following single low-dose cyclophosphamide treatment). Using STn-conjugated human serum albumin in a solid-phase enzyme-linked immunosorbent assay, it was shown that all patients developed IgM and IgG specific for the synthetic STn hapten. Following immunization, most patients were shown to develop increased titres of complement-mediated cytotoxic antibodies, partially inhibited by synthetic STn hapten, but not by the related TF hapten. We also detected IgM and IgG antibodies reactive with natural STn determinants expressed on ovine submaxillary mucin, the STn specificity of this reactivity being confirmed by hapten inhibition. Evaluation of clinical efficacy in a small pilot study is difficult. Five patients are alive 12 or more months after entry, and another 4 patients are alive 6 or more months after entry into the study. All 3 patients with known widespread bulky disease progressed despite ASI, 2 having died from widespread cancer. Two patients had partial responses, each lasting 6 months. While several patients had disease stability for 3-10 months, 1 patient with pulmonary metastases remains stable 15 months after entry into the program.

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“…STn antigen is an epitope of mucin that in high levels is known to be associated with poor prognosis in patients with cancer. [44,45] It also is a target for antibody-dependent cellular cytotoxicity. [46] The STn antigen is conjugated to the carrier keyhole limpet hemocyanin (KLH) and administered in the adjuvant Detox-B SE.…”

Section: Monoclonal Antibodiesmentioning

confidence: 99%

Frontiers of Ovarian Cancer Therapy

Balat

Mohammed²,

Kudelka³

et al. 1996

Cancer Control

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Since the majority of patients with ovarian cancer present with advanced stages of disease, more effective systemic approaches are needed to add to the benefits of surgical staging and debulking. New combinations of taxoids with cisplatin have prolonged survival, and other chemotherapeutic agents are being evaluated. Immunotherapy, including intraperitoneal approaches with monoclonal antibodies, cellular therapies and vaccines, hormone therapy with well-known drugs such as tamoxifen, and gene therapy give promise for the future.

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Detection of polymorphic epithelial mucins in the serum of systemic breast cancer patients using the monoclonal antibody, NCRC-11

Cited by 20 publications

References 19 publications

Reactivity of an anti-(human gastric carcinoma) monoclonal antibody with core-related peptides of gastrointestinal mucin

Reactivity of an anti-(human gastric carcinoma) monoclonal antibody with core-related peptides of gastrointestinal mucin

Immunization of breast cancer patients using a synthetic sialyl-Tn glycoconjugate plus Detox adjuvant

Frontiers of Ovarian Cancer Therapy

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