Search results for " Tumor-Associated"

Specificity of human natural antibodies referred to as anti-Tn

2020

International audience; To understand the role of human natural IgM known as antibodies against the carbohydrate epitope Tn, the antibodies were isolated using GalNAcα−Sepharose affinity chromatography, and their specificity was profiled using microarrays (a glycan array printed with oligosaccharides and bacterial polysaccharides, as well as a glycopeptide array), flow cytometry, and inhibition ELISA. The antibodies bound a restricted number of GalNAcα-terminated oligosaccharides better than the parent monosaccharide, e.g., 6-O-Su-GalNAcα and GalNAcα1−3Galβ1−3(4)GlcNAcβ. The binding with several bacterial polysaccharides that have no structural resemblance to the affinity ligand GalNAcα was…

Immunization with a Synthetic Human MUC1 Glycopeptide Vaccine against Tumor-Associated MUC1 Breaks Tolerance in Human MUC1 Transgenic Mice.

2017

Breaking tolerance is crucial for effective tumor immunotherapy. We showed that vaccines containing tumor-associated human MUC1 glycopeptides induce strong humoral antitumor responses in mice. The question remained whether such vaccines work in humans, in systems where huMUC1 is a self-antigen. To clarify the question, mice transgenic in expressing huMUC1, mimicking the self-tolerant environment, and wild-type mice were vaccinated with a synthetic vaccine. This vaccine comprised STn and Tn antigens bound to a MUC1 tandem repeat peptide coupled to tetanus toxoid. The vaccine induced strong immune responses in wild-type and huMUC1-transgenic mice without auto-aggressive side effects. All anti…

Morphological, immunohistochemical and biochemical characterization of 6 newly established human ovarian carcinoma cell lines

1992

Six permanent human tumor cell lines (OV-MZ-1 to 6) were established from 6 patients with serous adenocarcinomas of the ovary. These cell lines were derived from both solid tumors and ascites, from pre-treated and untreated patients, and are available over a range of in vitro passage numbers. The tumor cells grow its monolayers and develop foci of “piled-up” cells in confluent cultures. Flow cytophotometry showed that all the lines exhibited DNA hyperdiploidy with DNA tetraploidy in one cell line and DNA aneuploidy in the other cell lines. The mean population doubling time ranged from 24 to 52 hr. Transmission electron microscopy demonstrated that the tumor cells of all cell lines exhibited…

Lysosomal aspartic and cysteine proteinases serum levels in patients with pancreatic cancer or pancreatitis

1997

Lysosomal cathepsins D (CD), B (CB), and L (CL) serum levels were determined by immunoassays in patients with chronic (CHP) or acute (AP) pancreatitis and in patients with ductal pancreatic carcinoma (DPC) and correlated with some biological and clinical parameters of this tumor. CB serum concentrations significantly higher than those measured in healthy subjects (NS) were observed in CHP, AP, and DPC patients (p < 0.01). However, no significant difference was noted among these groups. Increased CL serum levels were evident only in cancer patients compared to NS, AP, or CHP groups (p < 0.05), while no difference was observed among these groups. Elevated CD serum values were observed i…

Synthetic Antitumor Vaccines from Tetanus Toxoid Conjugates of MUC1 Glycopeptides with the Thomsen-Friedenreich Antigen and a Fluorine-Substituted An…

2010

Effects of interferon gamma on the proliferation and modulation of cell-surface structures of human ovarian carcinoma cell lines.

1993

Platinum-containing regimens are very effective in the primary treatment of ovarian cancer. However, upon subsequent treatment most tumors develop multidrug resistance. The clinical application of biological response modifiers like interferon gamma (IFN gamma) in advanced ovarian cancer is therefore of increasing interest. Permanent ovarian cancer cell lines are suitable for investigating the mode of action and the potential clinical effectiveness of such response modifiers. IFN gamma is known to modulate many cellular functions. In this study it was compared for its antiproliferative and antigen-modulatory activity on the expression of tumor-associated (CA-125, HMFG, CEA) and major histoco…

Droloxifene-Induced Spikes of Tumor Markers Predict Benefit of Therapy

1991

In the clinical monitoring of cancer, tumor marker proteins may reflect the status of the disease. In cases with radio- and chemotherapy, spikes of tumor markers were found shortly after starting the therapy. These spikes were interpreted as a sign of tumor lysis. Recently during therapy of breast cancer with the new antiestrogen droloxifene, spikes of CA 125 and CA 15-3 were also found in about one-third of patients responding to therapy. The peaks of these initial increases were recorded between 14 and 60 days after the onset of treatment, with maximum concentrations up to 1,890% of the initial value. Marker concentrations decreased thereafter, to new baselines at or below the initial val…

T cells engineered to express a T-cell receptor specific for glypican-3 to recognize and kill hepatoma cells in vitro and in mice

2015

Background & Aims Cancer therapies are being developed based on our ability to direct T cells against tumor antigens. Glypican-3 (GPC3) is expressed by 75% of all hepatocellular carcinomas (HCC), but not in healthy liver tissue or other organs. We aimed to generate T cells with GPC3-specific receptors that recognize HCC and used them to eliminate GPC3-expressing xenograft tumors grown from human HCC cells in mice. Methods We used mass spectrometry to obtain a comprehensive peptidome from GPC3-expressing hepatoma cells after immune-affinity purification of human leukocyte antigen (HLA)-A2 and bioinformatics to identify immunodominant peptides. To circumvent GPC3 tolerance resulting from feta…

Fully synthetic self-adjuvanting thioether-conjugated glycopeptide-lipopeptide antitumor vaccines for the induction of complement-dependent cytotoxic…

2012

Glycopeptides of tumor-associated mucin MUC1 are promising target structures for the development of antitumor vaccines. Because these endogenous structures were weakly immunogenic, they were coupled to immune-response-stimulating T-cell epitopes and the Pam(3)Cys lipopeptide to induce strong immune responses in mice. A new thioether-ligation method for the synthesis of two- and three-component vaccines that contain MUC1 glycopeptides as the B-cell epitopes, a T-cell epitope peptide, and the Pam(3)CSK(4) lipopeptide is described. The resulting fully synthetic vaccines were used for the vaccination of mice, either in a liposome with Freund's adjuvant or in aqueous PBS buffer. The three-compon…

Fluorinated glycosyl amino acids for mucin-like glycopeptide antigen analogues.

2010

The aberrant glycosylation profiles of mucin glycoproteins on epithelial tumour cells represent attractive target structures for the development of immunotherapy against cancer. Mucin-type glycopeptides have been successfully investigated as molecularly defined vaccine prototypes for triggering humoral immunity but are susceptible to rapid in vivo degradation. As a potential means to enhance the bioavailabilities of the antigenic structures, hydrolysis-resistant carbohydrate analogues with fluorine substituents at positions C6, C2' and C6' were synthesised and incorporated into the tandem repeat sequence of the mucin MUC1. The resulting pseudo-glycopeptides can be used to elucidate the effe…