Search results for " Tumor-Associated"
showing 10 items of 20 documents
Synthesis of tumor-associated glycopeptide antigens.
2002
Carbohydrates and peptides linked together in glycoproteins constitute important components of the molecular communication between cells in multicellular organisms. Cell morphogenesis and tumorigenesis are accompanied by changes in the glycoprotein profiles of the outer cell membranes. Glycopeptide fragments of glycoproteins that have altered structures in tumor cells are of interest as tumor-associated antigens for the distinction between normal cells and tumor cells. In contrast to glycoproteins isolated from biological sources, synthetic glycopeptides are obtained in pure form and exactly specified structures. The methods developed for the synthesis of glycopeptides with tumor-associated…
Tuning tumor-specific T-cell activation: a matter of costimulation?
2002
Abstract The stimulation of a specific antitumor immune response, involving the recruitment of T cells and induction of T-cell effector functions, is an attractive possibility for cancer immunotherapy. In the past few years, advances in our understanding of the mechanisms of T-cell activation and costimulation have provided the basis for strategies to enhance antitumor immunity and break tolerance. These strategies include the equipment of tumor cells with costimulatory molecules such as B7, blockade of inhibitory signals on T cells (e.g. through cytotoxic T-lymphocyte antigen 4) and grafting of T cells with antigen-triggered, recombinant costimulatory receptors. Combining antigen-triggered…
Chemoenzymatic synthesis of O-glycopeptides carrying the tumor associated TN-antigen structure
1993
Abstract The application of the lipase-catalyzed C-terminal deprotection of heptyl esters for the construction of acid- and base-labile O -glycopeptides carrying the characteristic structural element of the tumor associated T N -antigen (GalNAc α→Ser/Thr) is described
PD-1, PD-L1, and CD163 in pancreatic undifferentiated carcinoma with osteoclast-like giant cells: A expression patterns and clinical implications
2018
Undifferentiated carcinoma with osteoclast-like giant cells (UCOGC), a variant of pancreatic ductal adenocarcinoma (PDAC), has a striking genetic similarity to PDAC but a significantly improved overall survival. We hypothesize that this difference could be due to the immune response to the tumor, and as such, we investigated the expression of PD-1, PD-L1, and CD163 in a series of UCOGC. To this aim, 27 pancreatic UCOGCs (11 pure and 16 PDAC-associated), 5 extrapancreatic tumors with osteoclast-like giant cells and 10 pancreatic anaplastic carcinomas were immunostained using antibodies against PD-1, PD-L1, and CD163. In pancreatic UCOGCs, PD-L1 was expressed in neoplastic cells of 17 (63%) o…
Towards a fully synthetic MUC1-based anticancer vaccine: efficient conjugation of glycopeptides with mono-, di-, and tetravalent lipopeptides using c…
2011
Abstract The membrane-bound tumor-associated glycoprotein MUC1 is aberrantly glycosylated in cancer cells compared with normal cells, and is therefore considered an attractive target for cancer immunotherapy. However, tumor-associated glycopeptides from MUC1 do not elicit a sufficiently robust immune response. Therefore, antitumor vaccines were developed, which consist of MUC1 glycopeptides as the B epitopes and immune-stimulating toll-like receptor 2 (TLR 2) lipopeptide ligands. These fully synthetic vaccine candidates were prepared by solid-phase synthesis of the MUC1 glycopeptides. The Pam(3) Cys lipopeptide, also synthesized on solid-phase, was C-terminally coupled to oligovalent lysine…
Synthesis of tumor-associated glycopeptide antigens for the development of tumor-selective vaccines
2004
In contrast to normal cells, the glycoprotein profile on epithelial tumor cells is distinctly altered. Due to an incomplete formation of the glycan side-chains resulting from a premature sialylation, additional peptide epitopes become accessible to the immune system in mucin-type glycoproteins on tumor cells. These tumor-associated structure alterations constitute the basis for a selective immunological attack on cancer cells. For the construction of immunostimulating antigens, glycopeptide partial structures from the mucins MUC1 and MUC4 carrying the tumor-associated sialyl-T(N), alpha2,6-sialyl-T and alpha2,3-sialyl-T antigens have been synthesized. Employing different linkers such as the…
Synthesis of fluorinated Thomsen-Friedenreich antigens: direct deoxyfluorination of αGalNAc-threonine tert-butyl esters.
2011
Selectively 6-fluorinated analogs of the tumor-associated T(N) antigen Fmoc-Thr(α-O-GalNAc)-OtBu can be efficiently prepared using DAST-mediated de(hydr)oxyfluorination reactions of preformed and orthogonally protected glycosyl amino esters without affecting the labile protecting groups and O-glycosidic linkages. The resulting mono- and difluorinated T(N) analogs are interesting building blocks for non-hydrolyzable mucin-type antigen mimetics, as illustrated by the unprecedented synthesis of two different multiply fluorinated Thomsen-Friedenreich derivatives. The reported deoxyfluoro antigen analogs represent important functional probes for carbohydrate-binding proteins and glycosyl-process…
Synthesis of a MUC1-glycopeptide-BSA conjugate vaccine bearing the 3'-deoxy-3'-fluoro-Thomsen-Friedenreich antigen.
2011
A novel MUC1-glycopeptide–BSA conjugate vaccine with a specifically fluorinated Thomsen–Friedenreich antigen side chain at Thr6 was prepared. Preliminary immunological experiments reveal specific binding of the tumor-associated glycopeptide antigen analog by anti-MUC1-mouse antibodies.
The role of the Thomsen-Friedenreich antigen as a tumor-associated molecule.
1990
The Thomsen-Friedenreich antigen (Gal-GalNAc) represents a tumor-associated molecule, which is assumed to be one of the few chemically well-defined antigens with a proven association with malignancy. In order to analyze the role of the carbohydrate structure Gal-GalNAc for gastrointestinal tumors, we immunized Balb/c mice with MCF-7 breast tumor cells together with synthetic Gal-GalNAc linked to a BSA carrier. One monoclonal antibody (82-A6) was established which recognizes the Thomsen-Friedenreich antigen according to the biochemical and serological analysis presented here. In contrast to the studies performed in the past, immunohistochemical results using this antibody 82-A6 did not exhib…
Estradiol, progesterone, 17-hydroxyprogesterone, androstenedione and CA125 in patients with ovarian carcinoma.
1992
Estradiol, progesterone, 17-hydroxyprogesterone, androstenedione and CA125 were assayed in 25 women (12 oophorectomized before entering the study) with ovarian carcinoma. The data from patients were ordered according to the presence or absence of the gonads. The patients with ovaries (Group A) showed significantly higher levels of estradiol (p less than 0.01), progesterone (p less than 0.01) and 17-hydroxyprogesterone (p less than 0.01) than controls. This difference was not observed between oophorectomized patients (Group B) and controls. CA125 levels were significantly higher in patients that in controls (p less than 0.001) irrespective of the ovarian status of the patients. Eleven patien…