Effects of N-acetyl-glucosamine-coated glycodendrimers as biological modulators in the B16F10 melanoma model in vivo
Language English Country Greece Media print
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
12851676
Knihovny.cz E-resources
- MeSH
- Acetylglucosamine administration & dosage chemistry MeSH
- Antigens, Surface genetics metabolism MeSH
- Biocompatible Materials MeSH
- Killer Cells, Natural immunology MeSH
- Antigens, CD metabolism MeSH
- CD4-Positive T-Lymphocytes immunology MeSH
- CD8-Positive T-Lymphocytes immunology MeSH
- Cytokines metabolism MeSH
- Cytotoxicity, Immunologic MeSH
- Dendrimers MeSH
- Fluorescent Dyes MeSH
- Glycoconjugates administration & dosage chemistry MeSH
- NK Cell Lectin-Like Receptor Subfamily B MeSH
- Lectins, C-Type genetics metabolism MeSH
- Melanoma, Experimental immunology pathology MeSH
- Mice, Inbred C57BL MeSH
- Mice MeSH
- Tumor Cells, Cultured MeSH
- Polyamines administration & dosage MeSH
- Recombinant Proteins genetics metabolism MeSH
- Dose-Response Relationship, Drug MeSH
- Animals MeSH
- Check Tag
- Male MeSH
- Mice MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Acetylglucosamine MeSH
- Antigens, Surface MeSH
- Biocompatible Materials MeSH
- Antigens, CD MeSH
- Cytokines MeSH
- Dendrimers MeSH
- Fluorescent Dyes MeSH
- Glycoconjugates MeSH
- NK Cell Lectin-Like Receptor Subfamily B MeSH
- Lectins, C-Type MeSH
- PAMAM Starburst MeSH Browser
- Polyamines MeSH
- Recombinant Proteins MeSH
Glyco-coat changes on cancer cells due to aberrant glycosylation are potential targets for immune recognition through lectin-like receptors on immune cells. These cells include natural killer (NK), CD8+ and CD4+ lymphocytes, all reported to have, together with cytokines, important functions in antitumor immunity. The aim of this study was to evaluate a possible role of synthetic monodisperse multivalent neo-glycoconjugates, namely glycodendrimers, as a new approach to anticancer immune modulation through carbohydrate-mediated immune recognition. Octavalent polyamidoamine dendrimers functionalized with N-acetyl-glucosamine residues (PAMAM-GlcNAc8), with in vitro high affinity for the recombinant lymphocyte receptor NKR-P1A, were employed. To follow the fate of the compound, a fluorescent marker was conjugated to the tetra-branched semi-component of the dendrimer. Tumor development and immunity were evaluated in C57BL/6 mice. Animals were inoculated with B16F10 melanoma cells and underwent different protocols of PAMAM-GlcNAc8 administration. Advantages on survival and reduction of tumor growth were obtained in dose-dependent manner, by IP route. Increase of CD69+ cells in the spleen and their appearance inside the tumors, early progressive release of IL-1beta, a later production of INFgamma and IL-2 concomitant to an increment of CD4+ cells were observed. Cytotoxicity assays, performed ex vivo, showed an enhanced NK cell activity proportioned to the percentage of activated NK cells. Our data suggest that well-defined multivalent neo-glycoconjugates can stimulate an antitumor immune response engaging both innate and acquired immunity.
Int J Oncol. 2014 Apr;44(4):1410 PubMed
Nkrp1 family, from lectins to protein interacting molecules
