14 results on '"Zuzana Antosova"'
Search Results
2. SOT101 induces NK cell cytotoxicity and potentiates antibody-dependent cell cytotoxicity and anti-tumor activity
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Zuzana Antosova, Nada Podzimkova, Jakub Tomala, Katerina Augustynkova, Katerina Sajnerova, Eva Nedvedova, Milada Sirova, Guy de Martynoff, David Bechard, Ulrich Moebius, Marek Kovar, Radek Spisek, and Irena Adkins
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NK cells ,antibody-dependent cytotoxicity ,interleukin-15 ,immunotherapy ,therapeutic antibodies ,RLI-15 ,Immunologic diseases. Allergy ,RC581-607 - Abstract
SOT101 is a superagonist fusion protein of interleukin (IL)-15 and the IL-15 receptor α (IL-15Rα) sushi+ domain, representing a promising clinical candidate for the treatment of cancer. SOT101 among other immune cells specifically stimulates natural killer (NK) cells and memory CD8+ T cells with no significant expansion or activation of the regulatory T cell compartment. In this study, we showed that SOT101 induced expression of cytotoxic receptors NKp30, DNAM-1 and NKG2D on human NK cells. SOT101 stimulated dose-dependent proliferation and the relative expansion of both major subsets of human NK cells, CD56brightCD16- and CD56dimCD16+, and these displayed an enhanced cytotoxicity in vitro. Using human PBMCs and isolated NK cells, we showed that SOT101 added concomitantly or used for immune cell pre-stimulation potentiated clinically approved monoclonal antibodies Cetuximab, Daratumumab and Obinutuzumab in killing of tumor cells in vitro. The anti-tumor efficacy of SOT101 in combination with Daratumumab was assessed in a solid multiple myeloma xenograft in CB17 SCID mouse model testing several combination schedules of administration in the early and late therapeutic setting of established tumors in vivo. SOT101 and Daratumumab monotherapies decreased with various efficacy tumor growth in vivo in dependence on the advancement of the tumor development. The combination of both drugs showed the strongest anti-tumor efficacy. Specifically, the sequencing of both drugs did not matter in the early therapeutic setting where a complete tumor regression was observed in all animals. In the late therapeutic treatment of established tumors Daratumumab followed by SOT101 administration or a concomitant administration of both drugs showed a significant anti-tumor efficacy over the respective monotherapies. These results suggest that SOT101 might significantly augment the anti-tumor activity of therapeutic antibodies by increasing NK cell-mediated activity in patients. These results support the evaluation of SOT101 in combination with Daratumumab in clinical studies and present a rationale for an optimal clinical dosing schedule selection.
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- 2022
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3. 562 SO-C101 induces NK cell cytotoxicity and potentiates antibody-dependent cell cytotoxicity and anti-tumor activity
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Zuzana Antosova, Marketa Jiratova, and Eva Nedvedova
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Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Published
- 2020
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4. Abstract 3510: SOT201 is a novel targeted IL-15Rbg agonist to alleviate PD-1-mediated immune cell suppression and potentiate anti-tumor efficacy
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Irena Adkins, Zuzana Antosova, Klara Danova, Kamila Hladikova, Katerina Augustynkova, Katerina Sajnerova, Nada Podzimkova, Pavel Marasek, Guy de Martynoff, David Bechard, Ulrich Moebius, and Radek Spisek
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Cancer Research ,Oncology - Abstract
SOT201 is a novel immunocytokine consisting of a monoclonal humanized, Fc silenced antibody against PD-1 fused to a covalent RLI-15 complex of a human IL-15 mutein linked to the high-affinity binding site of the IL-15Rα, the sushi+ domain. SOT201 is developed for immunotherapeutic treatment of various types of cancers. The activity of SOT201 is based on spatiotemporal reinvigorating of anti-tumor immune responses by disrupting co-inhibitory T-cell signaling by blocking PD-1 and synergistically activating adaptive as well as innate immunity by IL-15-mediated signaling via the IL-2/IL-15βγ receptor on T cells, NK, NKT, and γδ T cells. SOT201 showed a superior potentiation of T cell stimulation over pembrolizumab in mixed lymphocyte reaction in vitro. Studies in cynomolgus monkeys showed that decreased affinity of IL-15 mutein in SOT201 for its IL-15Rβγ is well optimized to ensure favorable pharmacokinetic properties while inducing strong CD8+ T cell and NK cell activation and expansion. Synergistic action on CD8+ T cell activation of both anti-PD-1 and RLI-15 moieties was confirmed using mouse surrogate SOT201 molecules in vivo. Strong anti-tumor efficacy after SOT201 treatment was achieved in a human PD-1 transgenic mouse model implanted with the MC38-hPD-L1 cell line. These data represent a promising therapeutic candidate molecule leveraging the synergistic concerted action of anti-PD-1 blockage and simultaneous immune cell activation directed preferentially to the high PD-1+ T cell tumor environment. The therapeutic potential of SOT201 is currently being prepared for evaluation in a Phase I clinical study in metastatic advanced cancer patients as well as for PD-1 resistant/refractory patients as our clinical stage IL-2/IL-15Rβγ agonist SOT101 already showed a clinical benefit in these patients in its ongoing Phase I study. Citation Format: Irena Adkins, Zuzana Antosova, Klara Danova, Kamila Hladikova, Katerina Augustynkova, Katerina Sajnerova, Nada Podzimkova, Pavel Marasek, Guy de Martynoff, David Bechard, Ulrich Moebius, Radek Spisek. SOT201 is a novel targeted IL-15Rbg agonist to alleviate PD-1-mediated immune cell suppression and potentiate anti-tumor efficacy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3510.
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- 2022
5. 562 SO-C101 induces NK cell cytotoxicity and potentiates antibody-dependent cell cytotoxicity and anti-tumor activity
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David Bechard, Radek Spisek, Ulrich Moebius, Guy de Martynoff, Zuzana Antosova, Irena Adkins, Eva Nedvedova, Nada Podzimkova, and Marketa Jiratova
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Antibody-dependent cell-mediated cytotoxicity ,Chemistry ,medicine.drug_class ,Daratumumab ,Monoclonal antibody ,NKG2D ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,lcsh:RC254-282 ,Monoclonal ,Cancer cell ,Cancer research ,medicine ,Cytotoxic T cell ,CD8 - Abstract
Background SO-C101 is a superagonist fusion protein of interleukin (IL)-15 and the IL-15 receptor α (IL-15Rα) sushi+ domain, representing a promising clinical candidate for the treatment of cancer. SO-C101 specifically stimulates natural killer (NK) cells and memory CD8+ T cells with no significant expansion and activation of regulatory T cell compartment. Methods Human NK cell proliferation, the expression of NK cell receptors and ADCC activity of human PBMC after stimulation with SO-C101 in vitro in combination with monoclonal antibodies were detected by flow cytometry. The anti-tumor efficacy of SO-C101 in combination with Daratumumab was assessed in a multiple myeloma SCID xenograft mouse model in vivo. Results In this study, we show that SO-C101 induced proliferation and expansion of both major subsets of human NK cells, CD56brightCD16- and CD56dimCD16+. Furthermore, SO-C101 induced expression of the cytotoxic receptors NKp30 and NKG2D whereas no upregulation of the inhibitory receptors CD158a, CD158b and NKG2A was detected. Both NK cell subsets activated by SO-C101 exhibited cytotoxicity towards cancer cells in vitro. Using human PBMCs, we show that SO-C101 potentiated killing of tumor cells induced by several clinically approved therapeutic monoclonal antibodies such as Cetuximab, Daratumumab and Obinutuzumab in vitro. SO-C101 and Daratumumab monotherapy treatment inhibited tumor growth in vivo, however, their combination showed the strongest anti-tumor efficacy. Specifically, sequential administration of Daratumumab, followed by SO-C101 promoted complete tumor regression, compared to partial anti-tumor responses induced by the respective monotherapies. Conclusions SO-C101 augments the anti-tumor activity of therapeutic antibodies by increasing NK cells mediated antibody-dependent cell cytotoxicity. These results support the evaluation of SO-C101 in combination with monoclonal therapeutic antibodies in clinical studies. Ethics Approval The anti-tumor efficacy studies in mice were approved by the internal ethics board of the respective contract research organization (CRO).
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- 2020
6. Immobilization in polyvinyl alcohol hydrogel enhances yeast storage stability and reusability of recombinant laccase-producing S. cerevisiae
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Jana Zemančíková, Klára Herkommerová, Hana Sychrová, and Zuzana Antosova
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0106 biological sciences ,0301 basic medicine ,Preservation, Biological ,Saccharomyces cerevisiae ,Cell Culture Techniques ,Bioengineering ,01 natural sciences ,Applied Microbiology and Biotechnology ,Polyvinyl alcohol ,03 medical and health sciences ,chemistry.chemical_compound ,010608 biotechnology ,Debaryomyces hansenii ,Equipment Reuse ,Viability assay ,Food science ,Laccase ,Microbial Viability ,biology ,Chemistry ,Yarrowia ,General Medicine ,Cells, Immobilized ,biology.organism_classification ,Recombinant Proteins ,Yeast ,Enzyme assay ,030104 developmental biology ,Polyvinyl Alcohol ,biology.protein ,Biotechnology - Abstract
To improve the storage stability and reusability of various yeast strains and species by immobilization in polyvinyl alcohol (PVA) hydrogel particles. Debaryomyces hansenii, Pichia sorbitophila, Saccharomyces cerevisiae, Yarrowia lipolytica, and Zygosaccharomyces rouxii were immobilized in PVA particles using LentiKats technology and stored in sterile water at 4 °C. The immobilization improved the survival of all species; however, the highest storage stability was achieved for S. cerevisiae and Y. lipolytica which survived more than 1 year, in contrast to free cells that survived for only 3 months. Tests of the reusability of immobilized recombinant laccase-secreting S. cerevisiae revealed that the cells were suitable for repetitive use (55 cycles during 15 months) even after storage in water at 4 °C for 9 months. A suitable method for killing immobilized laccase-secreting cells without affecting the produced enzyme activity was also developed. The immobilization of yeasts in PVA hydrogel enables long-term, cheap storage with very good cell viability and productivity, thus becoming a promising approach for industrial applications.
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- 2017
7. Impingement heat transfer to the synthetic jet issuing from a nozzle with an oscillating cross section
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Zuzana Antosova and Zdenek Travnicek
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Jet (fluid) ,Materials science ,020209 energy ,Nozzle ,General Engineering ,Diaphragm (mechanical device) ,02 engineering and technology ,Mechanics ,Heat transfer coefficient ,Condensed Matter Physics ,01 natural sciences ,Nusselt number ,010305 fluids & plasmas ,Physics::Fluid Dynamics ,Heat flux ,0103 physical sciences ,Heat transfer ,Synthetic jet ,0202 electrical engineering, electronic engineering, information engineering - Abstract
This experimental study is focused on a rectangular synthetic (zero-net-mass-flux) jet impinging on a wall. The working fluid is air. A novel variant of a synthetic jet actuator (SJA) is proposed. Following biomimetic principles, the actuator incorporates a nozzle in which the cross-sectional area periodically oscillates during the driven cycle. Two independent actuating systems are used to drive the main SJA diaphragm (as seen in common SJAs with rigid nozzles) and the oscillating nozzle walls (unique to this study). Namely, the diaphragm is driven electrodynamically, and the nozzle walls are driven using a pair of piezoelectric transducers. The operating frequency of 62 Hz is selected by tuning both systems at their resonances. The nozzle slot width oscillates around an average value of approximately 6 mm. Four experimental methods were used: phase-locked visualization of the oscillating nozzle lips, direct measurement of the jet momentum flux using a precision scale, hot-wire anemometry, and an evaluation of the heat transfer coefficients on the exposed wall using heat flux sensors. The local distribution of the heat transfer coefficient on the wall (Nusselt number in a dimensionless form) indicated the three-dimensional character of the flow field with an axis-switching effect. It was concluded that the momentum flux and the heat transfer rate could be enhanced by the phase delay between the diaphragm and nozzle cycles. The reason is the fact that the nozzle cross-sectional area during the extrusion stroke is smaller than the area during the suction, thus the SJ velocity and momentum flux are promoted during extrusion while the losses are reduced during suction. The maximal effect was found at the phase shift of 270° for the ratio of the cross-section areas during the extrusion and suction of 0.74.
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- 2020
8. Efficient secretion of three fungal laccases from Saccharomyces cerevisiae and their potential for decolorization of textile industry effluent-A comparative study
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Iva Pichová, Hana Sychrová, Zuzana Antosova, and Klára Herkommerová
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0106 biological sciences ,0301 basic medicine ,Nitrogen ,Saccharomyces cerevisiae ,Biology ,Wastewater ,01 natural sciences ,03 medical and health sciences ,chemistry.chemical_compound ,010608 biotechnology ,Botany ,Coloring Agents ,Effluent ,Trametes versicolor ,Laccase ,Trametes ,Growth medium ,biology.organism_classification ,Culture Media ,030104 developmental biology ,Biochemistry ,chemistry ,Textile Industry ,Heterologous expression ,Oxidation-Reduction ,Biotechnology ,Myceliophthora thermophila - Abstract
Laccases are enzymes with a broad range of biotechnological applications and have, for example, the ability to oxidize many xenobiotics including synthetic dyes. In order to obtain an efficient laccase for the decolorization of dyes which spoil wastewater from the textile industry, genes encoding three various laccase enzymes were expressed in Saccharomyces cerevisiae. The expression of laccases from ascomycete Myceliophthora thermophila (MtL), and two basidiomycetes Trametes versicolor (TvL) and Trametes trogii (TtL) was optimized via selection of plasmids, promoters, media composition, and cultivation conditions. For the first time, the activity of the three secreted laccases was directly compared with the use of various substrates, including different dyes and a wastewater sample. A strong constitutive ADH1 promoter, minimal growth medium, optimized combination of copper and organic nitrogen source, and low cultivation temperature were shown to significantly increase the yields and relative activities of secreted laccases. Heterologous expression of three fungal laccases was successfully achieved in S. cerevisiae being the highest for MtL and the lowest for TvL. MtL, and particularly TtL, showed the decolorization capacity. This is the first report which compared decolorization of synthetic dyes and wastewater by several recombinant laccases and suggested MtL and TtL to be applicable in the ecofriendly enzymatic treatment of colored industry effluent. © 2017 American Institute of Chemical Engineers Biotechnol. Prog., 34:69-80, 2018.
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- 2017
9. Yeast Hosts for the Production of Recombinant Laccases: A Review
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Zuzana Antosova and Hana Sychrová
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0301 basic medicine ,Insecta ,Industrial production ,Production optimization ,Bioengineering ,Biology ,Protein Engineering ,Applied Microbiology and Biotechnology ,Biochemistry ,law.invention ,Substrate Specificity ,03 medical and health sciences ,Bioremediation ,law ,Yeasts ,Animals ,Molecular Biology ,Laccase ,Bacteria ,business.industry ,Fungi ,Yeast ,Recombinant Proteins ,Biotechnology ,030104 developmental biology ,Recombinant DNA ,Substrate specificity ,Biochemical engineering ,Heterologous expression ,business - Abstract
Laccases are multi-copper oxidoreductases which catalyze the oxidation of a wide range of substrates during the simultaneous reduction of oxygen to water. These enzymes, originally found in fungi, plants, and other natural sources, have many industrial and biotechnological applications. They are used in the food, textile, pulp, and paper industries, as well as for bioremediation purposes. Although natural hosts can provide relatively high levels of active laccases after production optimization, heterologous expression can bring, moreover, engineered enzymes with desired properties, such as different substrate specificity or improved stability. Hence, diverse hosts suitable for laccase production are reviewed here, while the greatest emphasis is placed on yeasts which are commonly used for industrial production of various proteins. Different approaches to optimize the laccase expression and activity are also discussed in detail here.
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- 2015
10. Therapeutic application of peptides and proteins: parenteral forever?
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Martina Mackova, Vladimír Král, Tomas Macek, and Zuzana Antosova
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Drug ,medicine.medical_specialty ,business.industry ,media_common.quotation_subject ,Biomedical Technology ,Proteins ,Bioengineering ,Pharmacology ,Bioavailability ,Route of administration ,Drug Delivery Systems ,Drug delivery ,Animals ,Humans ,Nanotechnology ,Nanobiotechnology ,Medicine ,Peptides ,business ,Intensive care medicine ,Biomedical technology ,Biotechnology ,Biotechnology industry ,media_common ,Transdermal - Abstract
Varied therapeutic peptides and proteins represent a rapidly growing part of marketed drugs and have an undisputed place alongside other established therapies. Nevertheless, such biodrugs have several drawbacks that hinder their therapeutic application. These are undesirable physicochemical properties, such as variable solubility, low bioavailability and limited stability. These issues can be overcome by addition of stabilizing agents and directed injectable administration, which can however result in low patient compliance. Hence, there is a drive in the biotechnology industry to produce needle-free and more user-friendly drugs, and this has led to the growth of nano-enabled drug delivery systems in the last decade. As discussed here, nanobiotechnology is becoming a commercially feasible and promising opportunity for oral, pulmonary and transdermal administration routes.
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- 2009
11. Isolation and study of the properties of recombinant pseudoosmotin
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Klara Richterova, Tereza Neubauerová, Martina Novakova, Martina Mackova, and Zuzana Antosova
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Isolation (health care) ,Biochemistry ,Chemistry ,law ,Recombinant DNA ,law.invention - Published
- 2011
12. Cloning the bacterial bphC gene into Nicotiana tabacum to improve the efficiency of phytoremediation of polychlorinated biphenyls
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Jitka Viktorova, Zuzana Antosova, Martina Mackova, Miklós Szekeres, Tomas Macek, Katerina Demnerova, and Martina Novakova
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Nicotiana tabacum ,Transgene ,Recombinant Fusion Proteins ,Green Fluorescent Proteins ,Bioengineering ,Genetically modified crops ,Biology ,Applied Microbiology and Biotechnology ,Dioxygenases ,chemistry.chemical_compound ,Bacterial Proteins ,Dioxygenase ,Tobacco ,Luciferase ,Cloning, Molecular ,Luciferases ,Gene ,Glucuronidase ,Cloning ,Genetics ,Burkholderiaceae ,fungi ,food and beverages ,biology.organism_classification ,Plants, Genetically Modified ,Polychlorinated Biphenyls ,Article Addendum ,Biodegradation, Environmental ,chemistry ,DNA ,Biotechnology - Abstract
The aim of this work was to construct transgenic plants with increased capabilities to degrade organic pollutants, such as polychlorinated biphenyls. The environmentally important gene of bacterial dioxygenase, the bphC gene, was chosen to clone into a plant of Nicotiana tabacum. The chosen bphC gene encodes 2,3-dihydroxybiphenyl-1,2-dioxygenase, which cleaves the aromatic ring of dihydroxybiphenyl, and we cloned it in fusion with the gene for β-glucuronidase (GUS), luciferase (LUC) or with a histidine tail. Several genetic constructs were designed and prepared and the possible expression of desired proteins in tobacco plants was studied by transient expression. We used genetic constructs successfully expressing dioxygenase's genes we used for preparation of transgenic tobacco plants by agrobacterial infection. The presence of transgenic DNA , mRNA and protein was determined in parental and the first filial generation of transgenic plants with the bphC gene. Properties of prepared transgenic plants will be further studied.
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- 2010
13. Heterologous expression of three laccases from different origin in Saccharomyces cerevisiae and their use for environmental applications
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Zuzana Antosova, Hana Sychrová, Iva Pichová, Jiri Dostal, and Klara Richterova
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Laccase ,Biochemistry ,biology ,Chemistry ,Saccharomyces cerevisiae ,Bioengineering ,General Medicine ,Heterologous expression ,biology.organism_classification ,Molecular Biology ,Biotechnology ,Microbiology - Published
- 2014
14. Control of a Round Jet Intermittency and Transition to Turbulence by Means of an Annular Synthetic Jet
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Zuzana Antošová and Zdeněk Trávníček
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flow intermittency ,flow control ,turbulence ,synthetic jet actuator ,coaxial jets ,annular synthetic jets ,Materials of engineering and construction. Mechanics of materials ,TA401-492 ,Production of electric energy or power. Powerplants. Central stations ,TK1001-1841 - Abstract
This paper deals with active control of a continuous jet issuing from a long pipe nozzle by means of a concentrically placed annular synthetic jet. The experiments in air cover regimes of laminar, transitional, and turbulent main jet flows (Reynolds number ranges 1082–5181). The velocity profiles (time-mean and fluctuation components) of unforced and forced jets were measured using hot-wire anemometry. Six flow regimes are distinguished, and their parameter map is proposed. The possibility of turbulence reduction by forcing in transitional jets is demonstrated, and the maximal effect is revealed at Re = 2555, where the ratio of the turbulence intensities of the forced and unforced jets is decreased up to 0.45.
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- 2021
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