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24 záznamů v Medvik Filtry

Článek

pH and ROS Responsiveness of Polymersome Nanovaccines for Antigen and Adjuvant Codelivery: An In Vitro and In Vivo Comparison

Jäger, Eliézer
Autor Jäger, Eliézer Institute of Macromolecular Chemistry, Academy of Sciences of the Czech Republic, Heyrovsky Sq. 2, 162 06 Prague, Czech Republic Department of Medical BioSciences, Radboud University Medical Center, Geert Grooteplein Zuid 28, 6525 GA Nijmegen, The Netherlands
Ilina, Olga
Autor Ilina, Olga Department of Medical BioSciences, Radboud University Medical Center, Geert Grooteplein Zuid 28, 6525 GA Nijmegen, The Netherlands
Dölen, Yusuf
Autor Dölen, Yusuf Department of Medical BioSciences, Radboud University Medical Center, Geert Grooteplein Zuid 28, 6525 GA Nijmegen, The Netherlands
Valente, Michael
Autor Valente, Michael Department of Medical BioSciences, Radboud University Medical Center, Geert Grooteplein Zuid 28, 6525 GA Nijmegen, The Netherlands
van Dinther, Eric A W
Autor van Dinther, Eric A W Department of Medical BioSciences, Radboud University Medical Center, Geert Grooteplein Zuid 28, 6525 GA Nijmegen, The Netherlands
Jäger, Alessandro
Autor Jäger, Alessandro Institute of Macromolecular Chemistry, Academy of Sciences of the Czech Republic, Heyrovsky Sq. 2, 162 06 Prague, Czech Republic
Figdor, Carl G
Autor Figdor, Carl G Department of Medical BioSciences, Radboud University Medical Center, Geert Grooteplein Zuid 28, 6525 GA Nijmegen, The Netherlands Institute for Chemical Immunology, Geert Grooteplein Zuid 28, 6525 GA Nijmegen, The Netherlands
Verdoes, Martijn
Autor Verdoes, Martijn ORCID Department of Medical BioSciences, Radboud University Medical Center, Geert Grooteplein Zuid 28, 6525 GA Nijmegen, The Netherlands Institute for Chemical Immunology, Geert Grooteplein Zuid 28, 6525 GA Nijmegen, The Netherlands

Biomacromolecules. 2024 ; 25 (3) : 1749-1758. [pub] 20240118

ISSN 1526-4602
Medvik
Zdroj

The antitumor immunity can be enhanced through the synchronized codelivery of antigens and immunostimulatory adjuvants to antigen-presenting cells, particularly dendritic cells (DCs), using nanovaccines (NVs). To study the influence of intracellular vaccine cargo release kinetics on the T cell activating capacities of DCs, we compared stimuli-responsive to nonresponsive polymersome NVs. To do so, we employed "AND gate" multiresponsive (MR) amphiphilic block copolymers that decompose only in response to the combination of chemical cues present in the environment of the intracellular compartments in antigen cross-presenting DCs: low pH and high reactive oxygen species (ROS) levels. After being unmasked by ROS, pH-responsive side chains are exposed and can undergo a charge shift within a relevant pH window of the intracellular compartments in antigen cross-presenting DCs. NVs containing the model antigen Ovalbumin (OVA) and the iNKT cell activating adjuvant α-Galactosylceramide (α-Galcer) were fabricated using microfluidics self-assembly. The MR NVs outperformed the nonresponsive NV in vitro, inducing enhanced classical- and cross-presentation of the OVA by DCs, effectively activating CD8+, CD4+ T cells, and iNKT cells. Interestingly, in vivo, the nonresponsive NVs outperformed the responsive vaccines. These differences in polymersome vaccine performance are likely linked to the kinetics of cargo release, highlighting the crucial chemical requirements for successful cancer nanovaccines.

MeSH
adjuvancia imunologická farmakologie MeSH
antigeny chemie MeSH
CD8-pozitivní T-lymfocyty MeSH
dendritické buňky MeSH
koncentrace vodíkových iontů MeSH
myši inbrední C57BL MeSH
myši MeSH
nanovakcíny * MeSH
ovalbumin MeSH
reaktivní formy kyslíku MeSH
vakcíny * chemie MeSH
zvířata MeSH
Check Tag
myši MeSH
zvířata MeSH
Publikační typ
časopisecké články MeSH

Článek

Beneficial Effect of Heat-induced Antigen Retrieval in Immunocytochemical Detection of Intracellular Antigens in Alcohol-fixed Cell Samples

Applied immunohistochemistry & molecular morphology. 2020 ; 28 (2) : 166-174. [pub] -

Appl. immunohistochem. mol. morphol. (Print)
ISSN 1533-4058
Medvik
Zdroj

Immunohistochemistry and immunocytochemistry (ICC) play an irreplaceable role in research and diagnostics. It is well known that antigen retrieval (AR) can, as a technique, have beneficial outcomes on immunohistochemistry results when using formalin-fixed, paraffin-embedded tissue samples. The main purpose of AR is to break protein crosslinks which are formed during formalin fixation. Although AR was originally designed for formalin-fixed, paraffin-embedded samples, the usefulness of AR in ICC has been described in previous studies. Cytologic samples are often fixed in alcohol-based fixatives which does not lead to the formation of crosslinks. Therefore, alcohol-fixed samples can be successfully immunostained without AR. We investigated the effect of heat-induced antigen retrieval (HIAR) on alcohol-fixed HEK293 cell line samples and patient cytologic samples from thyroid gland obtained by fine needle aspiration technique. We compared indirect 2-step ICC staining results performed according to the protocol with or without HIAR in citrate buffer pH 6 for several antibodies. Utilizing HIAR against intracellular antigens has beneficial effects. Therefore, more diluted antibodies can be used for satisfactory results. However, surface antigens were probably damaged by HIAR treatment. We demonstrated evident changes in cell surface topography after HIAR treatment by atomic force microscopy. Staining specificity of patient samples improves and background staining is reduced, allowing higher dilutions of primary antibody. Improving staining specificity is necessary for accurate diagnostics. Although we have shown the beneficial effect of HIAR for immunostaining intracellular antigens, proper staining protocol should be tested on appropriate controls for individual antibodies.

Článek

VDJdb: a curated database of T-cell receptor sequences with known antigen specificity

Nucleic acids research. 2018 ; 46 (D1) : D419-D427. [pub] 20180104

Nucleic Acids Res
ISSN 1362-4962
Medvik
Zdroj

The ability to decode antigen specificities encapsulated in the sequences of rearranged T-cell receptor (TCR) genes is critical for our understanding of the adaptive immune system and promises significant advances in the field of translational medicine. Recent developments in high-throughput sequencing methods (immune repertoire sequencing technology, or RepSeq) and single-cell RNA sequencing technology have allowed us to obtain huge numbers of TCR sequences from donor samples and link them to T-cell phenotypes. However, our ability to annotate these TCR sequences still lags behind, owing to the enormous diversity of the TCR repertoire and the scarcity of available data on T-cell specificities. In this paper, we present VDJdb, a database that stores and aggregates the results of published T-cell specificity assays and provides a universal platform that couples antigen specificities with TCR sequences. We demonstrate that VDJdb is a versatile instrument for the annotation of TCR repertoire data, enabling a concatenated view of antigen-specific TCR sequence motifs. VDJdb can be accessed at https://vdjdb.cdr3.net and https://github.com/antigenomics/vdjdb-db.

Článek

Complexes of streptavidin-fused antigens with biotinylated antibodies targeting receptors on dendritic cell surface: a novel tool for induction of specific T-cell immune responses

Molecular biotechnology. 2012 ; 51 (3) : 221-32.

Mol Biotechnol
ISSN 1559-0305
Medvik
Zdroj

The choice of tools that enable efficient targeting of exogenous antigens (Ag) for processing and presentation by professional Ag-presenting cells (APC) remains limited. This represents, indeed, a bottleneck in development of vaccines inducing specific T-cell responses. Here, we describe a novel strategy of Ag delivery into APCs. The Ag of choice is fused to the N- or C-terminus of streptavidin (SA) and tetrameric Ag-SA or SA-Ag fusion proteins are produced in E. coli and purified by 2-Iminobiotin-Agarose affinity chromatography. Alternatively, Ag-SA proteins are purified from urea extracts of E. coli inclusion bodies and refolded in vitro into functional tetramers. Complexes with biotinylated antibodies targeting cell surface receptors are formed and used to deliver the Ags of choice for processing and presentation by APCs and induction of Ag-specific CD4+ and CD8+ T-cell responses in vitro and in vivo.

MeSH
antigeny CD11c imunologie metabolismus MeSH
antigeny chemie genetika imunologie metabolismus MeSH
biotinylace MeSH
buněčné linie MeSH
dendritické buňky imunologie metabolismus MeSH
kur domácí MeSH
molekulární sekvence - údaje MeSH
myši inbrední C57BL MeSH
myši MeSH
ovalbumin chemie genetika imunologie metabolismus MeSH
receptory buněčného povrchu imunologie metabolismus MeSH
rekombinantní fúzní proteiny chemie genetika imunologie metabolismus MeSH
rozpustnost MeSH
sekvence aminokyselin MeSH
sekvence nukleotidů MeSH
streptavidin chemie genetika imunologie metabolismus MeSH
T-lymfocyty imunologie metabolismus MeSH
zvířata MeSH
Check Tag
myši MeSH
ženské pohlaví MeSH
zvířata MeSH
Publikační typ
časopisecké články MeSH
práce podpořená grantem MeSH

Článek

A possible crystal volume factor in the impact sensitivities of some energetic compounds

Journal of molecular modeling. 2010 ; 16 (5) : 895-901.

J Mol Model
ISSN 0948-5023
Medvik
Zdroj

We have investigated the possibility of a link between the impact sensitivities of energetic compounds and the space available to their molecules in their crystal lattices. As a measure of this space, we use Delta V=V(eff)-V(0.002), where V(eff) is the effective molecular volume obtained from the crystal density and V(0.002) is that enclosed by the 0.002 au contour of the molecule's gas phase electronic density, determined computationally. When experimental impact sensitivity was plotted against Delta V for a series of 20 compounds, the nitramines formed a separate group showing little dependence upon Delta V. Their impact sensitivities correlate well with an anomalous imbalance in the electrostatic potentials on their molecular surfaces, which is characteristic of energetic compounds in general. The imbalance is symptomatic of the weakness of the N-NO(2) bonds, caused by depletion of electronic charge. The impact sensitivities of non-nitramines, on the other hand, depend much more strongly upon Delta V, and can be quite effectively related to it if an electrostatically-based correction term is included.

Článek

Glycopeptide dendrimers. Part I

Journal of peptide science. 2008 ; 14 (1) : 2-43.

J Pept Sci
ISSN 1075-2617
Medvik
Zdroj

Glycopeptide dendrimers are branched structures containing both carbohydrates and peptides. Various classes of these compounds differing in composition and structure are mentioned, together with their practical use spanning from catalysis, transport vehicles to synthetic vaccines. The main stress is given to glycopeptide dendrimers, namely multiple antigen glycopeptides (MAGs). In MAGs, the core, branches or both are composed of amino acids or peptides. Other classes of glycodendrimers (PAMAM, polypropylene imine, cyclodextrin, calixarene, etc.) are mentioned too, but to a smaller extent. Their syntheses, physicochemical properties and biological activities are given with many examples. Glycopeptide dendrimers can be used as inhibitors of cell surface protein-carbohydrate interactions, intervention with bacterial adhesion, for studying of recognition processes, diagnostics, imaging and contrast agents, mimetics, for complexation of different cationts, as site-specific molecular delivery systems, for therapeutic purposes, as immunodiagnostics and in drug design. Biomedical applications of glycopeptide dendrimers as drug and gene delivery systems are also given.

Článek

Glycopeptide dendrimers. Part II

Journal of peptide science. 2008 ; 14 (1) : 44-65.

J Pept Sci
ISSN 1075-2617
Medvik
Zdroj

Glycopeptide dendrimers are regularly branched structures containing both carbohydrates and peptides. Various types of these compounds differing in composition and structure are mentioned, together with their practical use spanning from catalysis, transport vehicles to synthetic vaccines. This Part II (for Part I see JeZek J, et al., J. Pept. Sci. 2008; 14: 2-43) covers linear oligomers with variable valency (brush dendrimers, comb dendrimers), sequential oligopeptide carriers SOCn-I and SOCn-II, chitosan-based dendrimers, and brush dendrimers. Other types of glycopeptide dendrimers are self-immolative dendrimers (cascade release dendrimers, domino dendrimers), dendrimers containing omega-amino acids (Gly, beta-Ala, gamma-Abu and epsilon-aminohexanoic acid), etc. Microwave-assisted synthesis of dendrimers and libraries of glycopeptides and glycopeptide dendrimers are also included. Characterization of dendrimers by electromigration methods, mass spectrometry, and time-resolved and nonlinear optical spectroscopy, etc. plays an important role in purity assessment and structure characterization. Physicochemical properties of dendrimers including chirality are given. Stability of dendrimers, their biocompatibility and toxicity are reviewed. Finally, biomedical applications of dendrimers including imaging agents (contrast agents), site-specific drug delivery systems, artificial viruses, synthetic antibacterial, antiviral, and anticancer vaccines, inhibitors of cell surface protein-carbohydrate interactions, intervention with bacterial adhesion, etc. are given. Glycopeptide dendrimers were used also for studying recognition processes, as diagnostics and mimetics, for complexation of different cations, for therapeutic purposes, as immunodiagnostics, and in drug design.