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Article ; Online: CD40 stimulation via CD40 ligand enhances adenovirus-mediated tumour immunogenicity including 'find-me', 'eat-me', and 'kill-me' signalling.

Naseri, Sedigheh / Cordova, Mariela Mejia / Wenthe, Jessica / Lövgren, Tanja / Eriksson, Emma / Loskog, Angelica / Ullenhag, Gustav J

Journal of cellular and molecular medicine

2024 Volume 28, Issue 7, Page(s) e18162

Abstract: Immunostimulatory gene therapy using oncolytic viruses is currently evaluated as a promising therapy for cancer aiming to induce anti-tumour immunity. Here, we investigate the capacity of oncolytic adenoviruses (LOAd) and their transgenes to induce ... ...

Abstract	Immunostimulatory gene therapy using oncolytic viruses is currently evaluated as a promising therapy for cancer aiming to induce anti-tumour immunity. Here, we investigate the capacity of oncolytic adenoviruses (LOAd) and their transgenes to induce immunogenicity in the infected tumour cells. Oncolysis and death-related markers were assessed after infection of eight human solid cancer cell lines with different LOAd viruses expressing a trimerized, membrane-bound (TMZ)-CD40L, TMZ-CD40L and 41BBL, or no transgenes. The viruses induced transgene expression post infection before they were killed by oncolysis. Death receptors TRAIL-R1, TRAIL-R2 and Fas as well as immunogenic cell death marker calreticulin were upregulated in cell lines post infection. Similarly, caspase 3/7 activity was increased in most cell lines. Interestingly, in CD40
MeSH term(s)	Humans ; CD40 Ligand/genetics ; Adenoviridae/genetics ; B7-H1 Antigen/genetics ; Calreticulin/genetics ; CD40 Antigens ; Neoplasms
Chemical Substances	CD40 Ligand (147205-72-9) ; B7-H1 Antigen ; Calreticulin ; CD40 Antigens
Language	English
Publishing date	2024-03-17
Publishing country	England
Document type	Journal Article
ZDB-ID	2074559-X
ISSN	1582-4934 ; 1582-4934 ; 1582-1838
ISSN (online)	1582-4934
ISSN	1582-4934 ; 1582-1838
DOI	10.1111/jcmm.18162
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Article ; Online: A moment just for me - parents' experiences of an intervention for person-centred information in paediatric oncology.

Ringnér, Anders / Olsson, Cecilia / Eriksson, Emma / From, Ida / Björk, Maria

European journal of oncology nursing : the official journal of European Oncology Nursing Society

2021 Volume 51, Page(s) 101923

Abstract: Purpose: Information can help parents of children with cancer by reducing uncertainty and giving them a sense of control in a chaotic situation. Although providing information to parents is a core activity of paediatric oncology nursing, few studies ... ...

Abstract	Purpose: Information can help parents of children with cancer by reducing uncertainty and giving them a sense of control in a chaotic situation. Although providing information to parents is a core activity of paediatric oncology nursing, few studies focus on interventions for informing parents. Thus, the aim of this study is to evaluate parents' experiences after participating in a person-centred information intervention for parents of children with cancer. Method: This study is part of a process evaluation of a person-centred informational intervention in paediatric oncology for patients' parents. Qualitative semi-structured interviews with 13 parents who had taken part in the intervention were analysed using qualitative content analysis. Results: An opening for healing emerged as the overarching theme, consisting of three categories. Gaining a deeper understanding of the entire situation describes how parents benefitted from processing current topics and moving forward by learning. Caring reflections in a safe space describes how parents appreciated having a moment just for themselves and feeling better by venting their feelings. Meeting a competent and compassionate nurse describes how parents experienced trust and being listened to. Conclusion: Having individual information meetings integrated as a primary nursing responsibility, mediated by competent and compassionate nurses also responsible for the care of the child, could enhance person-centred care and individualise parental education.
MeSH term(s)	Adolescent ; Adult ; Aged ; Child ; Child, Preschool ; Communication ; Female ; Humans ; Male ; Middle Aged ; Neoplasms/nursing ; Nursing Evaluation Research ; Oncology Nursing/methods ; Parents/psychology ; Patient Satisfaction ; Pediatric Nursing/methods ; Professional-Family Relations ; Qualitative Research
Language	English
Publishing date	2021-02-12
Publishing country	Scotland
Document type	Journal Article ; Randomized Controlled Trial
ZDB-ID	2017117-1
ISSN	1532-2122 ; 1462-3889
ISSN (online)	1532-2122
ISSN	1462-3889
DOI	10.1016/j.ejon.2021.101923
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Article: A Comparison of Strategies to Improve Uptake of COVID-19 Vaccine among High-Risk Adults in Nairobi, Kenya in 2022.

Yego, Joan / Korom, Robert / Eriksson, Emma / Njavika, Sharon / Sane, Oulimata / Kanorio, Purity / Rotich, Oliver / Wambui, Stellah / Mureithi, Eunice

Vaccines

2023 Volume 11, Issue 2

Abstract: Background: COVID-19 vaccine uptake in Kenya is still low compared to other countries, especially in Europe and North America. In most parts of the country, a large percentage of the Kenyan population remains unvaccinated. As of October 2022, the ... ...

Abstract	Background: COVID-19 vaccine uptake in Kenya is still low compared to other countries, especially in Europe and North America. In most parts of the country, a large percentage of the Kenyan population remains unvaccinated. As of October 2022, the Ministry of Health (Kenya) estimates that only 36.2% of the adult population had been fully vaccinated. Methods: We conducted an experimental study in April 2022 targeting unvaccinated adults who had a history of hypertension and/or diabetes and those in the 60+ age group. We tested various messaging approaches using two different intervention channels. Results: Although the overall rate of vaccinated individuals according to national records is low, responses from the study group collected through phone call conversations show that higher-risk adults such as those older than 60 or those with chronic illnesses have a remarkably high vaccination rate of 89%. After the study, four participants received a COVID-19 vaccine within 1 month of the intervention. These four participants all received a loss-messaging intervention approach during the study. Conclusion: This study supports a national approach to increasing COVID-19 vaccination rates using loss-messaging directed at unvaccinated, high-risk individuals.
Language	English
Publishing date	2023-01-17
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2703319-3
ISSN	2076-393X
ISSN	2076-393X
DOI	10.3390/vaccines11020209
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Article ; Online: Immunostimulatory gene therapy targeting CD40, 4-1BB and IL-2R activates DCs and stimulates antigen-specific T-cell and NK-cell responses in melanoma models.

Wenthe, Jessica / Eriksson, Emma / Hellström, Ann-Charlotte / Moreno, Rafael / Ullenhag, Gustav / Alemany, Ramon / Lövgren, Tanja / Loskog, Angelica

Journal of translational medicine

2023 Volume 21, Issue 1, Page(s) 506

Abstract: Background: The activation of dendritic cells (DCs) is pivotal for generating antigen-specific T-cell responses to eradicate tumor cells. Hence, immunotherapies targeting this interplay are especially intriguing. Moreover, it is of interest to modulate ... ...

Abstract	Background: The activation of dendritic cells (DCs) is pivotal for generating antigen-specific T-cell responses to eradicate tumor cells. Hence, immunotherapies targeting this interplay are especially intriguing. Moreover, it is of interest to modulate the tumor microenvironment (TME), as this harsh milieu often impairs adaptive immune responses. Oncolytic viral therapy presents an opportunity to overcome the immunosuppression in tumors by destroying tumor cells and thereby releasing antigens and immunostimulatory factors. These effects can be further amplified by the introduction of transgenes expressed by the virus. Methods: Lokon oncolytic adenoviruses (LOAd) belong to a platform of chimeric serotype Ad5/35 viruses that have their replication restricted to tumor cells, but the expression of transgenes is permitted in all infected cells. LOAd732 is a novel oncolytic adenovirus that expresses three essential immunostimulatory transgenes: trimerized membrane-bound CD40L, 4-1BBL and IL-2. Transgene expression was determined with flow cytometry and ELISA and the oncolytic function was evaluated with viability assays and xenograft models. The activation profiles of DCs were investigated in co-cultures with tumor cells or in an autologous antigen-specific T cell model by flow cytometry and multiplex proteomic analysis. Statistical differences were analyzed with Kruskal-Wallis test followed by Dunn's multiple comparison test. Results: All three transgenes were expressed in infected melanoma cells and DCs and transgene expression did not impair the oncolytic activity in tumor cells. DCs were matured post LOAd732 infection and expressed a multitude of co-stimulatory molecules and pro-inflammatory cytokines crucial for T-cell responses. Furthermore, these DCs were capable of expanding and stimulating antigen-specific T cells in addition to natural killer (NK) cells. Strikingly, the addition of immunosuppressive cytokines TGF-β1 and IL-10 did not affect the ability of LOAd732-matured DCs to expand antigen-specific T cells and these cells retained an enhanced activation profile. Conclusions: LOAd732 is a novel immunostimulatory gene therapy based on an oncolytic adenovirus that expresses three transgenes, which are essential for mediating an anti-tumor immune response by activating DCs and stimulating T and NK cells even under imunosuppressive conditions commonly present in the TME. These qualities make LOAd732 an appealing new immunotherapy approach.
MeSH term(s)	Humans ; T-Lymphocytes ; Proteomics ; Melanoma/genetics ; Melanoma/therapy ; Killer Cells, Natural ; Cytokines/metabolism ; Genetic Therapy ; Dendritic Cells ; Tumor Microenvironment
Chemical Substances	Cytokines
Language	English
Publishing date	2023-07-27
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2118570-0
ISSN	1479-5876 ; 1479-5876
ISSN (online)	1479-5876
ISSN	1479-5876
DOI	10.1186/s12967-023-04374-2
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Article ; Online: Transferability of Human and Environmental Microbiome on Clothes as a Tool for Forensic Investigations.

Procopio, Noemi / Sguazzi, Giulia / Eriksson, Emma V / Ogbanga, Nengi / McKell, Frazer C / Newton, Eleanor P / Magni, Paola A / Bonicelli, Andrea / Gino, Sarah

Genes

2024 Volume 15, Issue 3

Abstract: Considering the growing importance of microbiome analyses in forensics for identifying individuals, this study explores the transfer of the skin microbiome onto clothing, its persistence on fabrics over time, and its transferability from the environment ... ...

Abstract	Considering the growing importance of microbiome analyses in forensics for identifying individuals, this study explores the transfer of the skin microbiome onto clothing, its persistence on fabrics over time, and its transferability from the environment and between different garments. Furthermore, this project compares three specific QIAGEN microbiome extraction kits to test their extraction efficiency on fabric samples. Additionally, this study aims to check if these extracts contain human DNA, providing a chance to obtain more information from the same evidence for personal identification. The results obtained show: (1) variations in the skin microbiome between the volunteers, potentially due to their different sex; (2) differences in microbial composition between worn and unworn clothing; (3) the influence of the environment on the microbial signature of unworn clothing; (4) the potential use of certain phyla as biomarkers to differentiate between worn and unworn garments, even over extended periods; (5) a tendency towards extraction biases in the QIAampMP
MeSH term(s)	Humans ; Clothing ; Skin ; DNA, Ribosomal ; Microbiota/genetics
Chemical Substances	DNA, Ribosomal
Language	English
Publishing date	2024-03-19
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2527218-4
ISSN	2073-4425 ; 2073-4425
ISSN (online)	2073-4425
ISSN	2073-4425
DOI	10.3390/genes15030375
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Article: Systemic immunity upon local oncolytic virotherapy armed with immunostimulatory genes may be supported by tumor-derived exosomes.

Labani-Motlagh, Alireza / Naseri, Sedigheh / Wenthe, Jessica / Eriksson, Emma / Loskog, Angelica

Molecular therapy oncolytics

2021 Volume 20, Page(s) 508–518

Abstract: Immunostimulatory gene therapy utilizing oncolytic viruses (OVs) as gene vehicles is a promising immunotherapy for cancer. Since viruses are immunogenic, systemic delivery can be troublesome due to neutralizing antibodies. Nevertheless, local delivery by ...

Abstract	Immunostimulatory gene therapy utilizing oncolytic viruses (OVs) as gene vehicles is a promising immunotherapy for cancer. Since viruses are immunogenic, systemic delivery can be troublesome due to neutralizing antibodies. Nevertheless, local delivery by intratumoral injection seems to induce systemic immune reactions. In this study, we demonstrate a novel mechanism of action of armed OV therapy suggesting that exosomes released by tumor cells infected with armed OV may participate to activate the immune system and this may also support systemic immunity. Tumor cell-derived exosomes commonly exert immunosuppressive functions. We hypothesized that exosomes derived from OV-infected tumor cells may instead be immunostimulatory. Human melanoma cells were infected by OVs armed with costimulatory molecules CD40 ligand (CD40L) and 4-1BB ligand (4-1BBL). Exosomes were purified and investigated for the presence of CD40L/4-1BBL mRNA and protein, and for their capacity to stimulate immune responses. The results show that the exosomes cargo transgenes. The exosomes from CD40L/4-1BBL-expressing tumor cells, or the viruses themselves, could stimulate robust dendritic cell (DC) activation with an enhanced level of major histocompatibility complex (MHC) and costimulatory molecules. Hence, exosomes after OV infection can locally activate immune responses at the tumor site and encounter immune cells such as DCs.
Language	English
Publishing date	2021-02-17
Publishing country	United States
Document type	Journal Article
ISSN	2372-7705
ISSN	2372-7705
DOI	10.1016/j.omto.2021.02.007
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Article ; Online: Choice of cuvette material can influence spectroscopic leakage and permeability experiments with liposomes.

Eriksson, Emma K / Agmo Hernández, Víctor

Chemistry and physics of lipids

2018 Volume 215, Page(s) 63–70

Abstract: Liposome solute permeability experiments are widely performed to gain information about lipid membrane characteristics. Spectroscopic methods are often used for this purpose, usually monitoring the leakage of a self-quenching fluorescent dye (e.g., ... ...

Abstract	Liposome solute permeability experiments are widely performed to gain information about lipid membrane characteristics. Spectroscopic methods are often used for this purpose, usually monitoring the leakage of a self-quenching fluorescent dye (e.g., carboxyfluorescein, CF) from the liposomes. Hereby, we investigate the effect of liposome-cuvette interactions, a seldom considered detail, on the results obtained from liposomal permeability experiments. The spontaneous leakage of CF from liposomes with different surface properties and phase states is followed using quartz and polystyrene cuvettes, and the results are compared. It is shown that for most lipid compositions the leakage profiles vary notably between different cuvette materials. Reproducibility of the measurements also varies depending on the cuvettes used, with polystyrene providing with more robust results. To explain these observations, the interaction of liposomes with polystyrene and quartz-like surfaces was characterized with the help of the quartz crystal microbalance with dissipation monitoring (QCM-D). Our results show that, while liposomes seldom interact with polystyrene, quartz-liposome interactions are almost unavoidable and have a large impact on the leakage experiments mainly via two mechanisms: i) the rupturing of liposomes on the cuvette surface causing a fast release of encapsulated CF, and ii) the disruption of adsorbed liposomes caused by magnetic stirring. Depending on their composition, the liposomes interact in different ways with quartz, affecting thus the extent of each proposed mechanism. The experiments demonstrate the importance of considering the cuvette material when planning and conducting spectroscopic experiments with liposomes.
MeSH term(s)	Adsorption ; Fluoresceins/chemistry ; Fluorescent Dyes/chemistry ; Lipid Bilayers/chemistry ; Lipids/chemistry ; Liposomes/chemistry ; Permeability ; Polystyrenes/chemistry ; Quartz/chemistry ; Quartz Crystal Microbalance Techniques/instrumentation ; Spectrometry, Fluorescence/instrumentation ; Surface Properties
Chemical Substances	Fluoresceins ; Fluorescent Dyes ; Lipid Bilayers ; Lipids ; Liposomes ; Polystyrenes ; Quartz (14808-60-7) ; 6-carboxyfluorescein (3301-79-9)
Language	English
Publishing date	2018-08-01
Publishing country	Ireland
Document type	Journal Article
ZDB-ID	213869-4
ISSN	1873-2941 ; 0009-3084
ISSN (online)	1873-2941
ISSN	0009-3084
DOI	10.1016/j.chemphyslip.2018.07.006
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Article: Effect of ubiquinone-10 on the stability of biomimetic membranes of relevance for the inner mitochondrial membrane.

Eriksson, Emma K / Agmo Hernández, Víctor / Edwards, Katarina

Biochimica et biophysica acta. Biomembranes

2018 Volume 1860, Issue 5, Page(s) 1205–1215

Abstract: Ubiquinone-10 (Q10) plays a pivotal role as electron-carrier in the mitochondrial respiratory chain, and is also well known for its powerful antioxidant properties. Recent findings suggest moreover that Q10 could have an important membrane stabilizing ... ...

Abstract	Ubiquinone-10 (Q10) plays a pivotal role as electron-carrier in the mitochondrial respiratory chain, and is also well known for its powerful antioxidant properties. Recent findings suggest moreover that Q10 could have an important membrane stabilizing function. In line with this, we showed in a previous study that Q10 decreases the permeability to carboxyfluorescein (CF) and increases the mechanical strength of 1-palmitoyl-2-oleyl-sn-glycero-phosphocholine (POPC) membranes. In the current study we report on the effects exerted by Q10 in membranes having a more complex lipid composition designed to mimic that of the inner mitochondrial membrane (IMM). Results from DPH fluorescence anisotropy and permeability measurements, as well as investigations probing the interaction of liposomes with silica surfaces, corroborate a membrane stabilizing effect of Q10 also in the IMM-mimicking membranes. Comparative investigations examining the effect of Q10 and the polyisoprenoid alcohol solanesol on the IMM model and on membranes composed of individual IMM components suggest, moreover, that Q10 improves the membrane barrier properties via different mechanisms depending on the lipid composition of the membrane. Thus, whereas Q10's inhibitory effect on CF release from pure POPC membranes appears to be directly and solely related to Q10's lipid ordering and condensing effect, a mechanism linked to Q10's ability to amplify intrinsic curvature elastic stress dominates in case of membranes containing high proportions of palmitoyl-2-oleoyl-sn-glycero-3-phosphoethanolamine (POPE).
MeSH term(s)	Adsorption ; Biomimetic Materials/chemistry ; Biomimetic Materials/metabolism ; Cell Membrane Permeability/drug effects ; Lipid Bilayers/chemistry ; Lipid Bilayers/metabolism ; Membrane Lipids/chemistry ; Membrane Lipids/metabolism ; Mitochondrial Membranes/chemistry ; Mitochondrial Membranes/drug effects ; Mitochondrial Membranes/metabolism ; Phosphatidylethanolamines/chemistry ; Phosphatidylethanolamines/pharmacokinetics ; Terpenes/chemistry ; Terpenes/pharmacology ; Ubiquinone/pharmacokinetics ; Ubiquinone/pharmacology
Chemical Substances	Lipid Bilayers ; Membrane Lipids ; Phosphatidylethanolamines ; Terpenes ; 1-palmitoyl-2-oleoylphosphatidylethanolamine (10015-88-0) ; Ubiquinone (1339-63-5) ; solanesol (FF31XTR2N4) ; Ubiquinone Q2 (I7T5V2W47R)
Language	English
Publishing date	2018-02-19
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	60-7
ISSN	1879-2596 ; 1879-260X ; 1872-8006 ; 1879-2642 ; 1879-2618 ; 1879-2650 ; 0005-2736 ; 0006-3002 ; 0005-2728 ; 0304-4165 ; 0167-4838 ; 1388-1981 ; 0167-4889 ; 0167-4781 ; 0304-419X ; 1570-9639 ; 0925-4439 ; 1874-9399
ISSN (online)	1879-2596 ; 1879-260X ; 1872-8006 ; 1879-2642 ; 1879-2618 ; 1879-2650
ISSN	0005-2736 ; 0006-3002 ; 0005-2728 ; 0304-4165 ; 0167-4838 ; 1388-1981 ; 0167-4889 ; 0167-4781 ; 0304-419X ; 1570-9639 ; 0925-4439 ; 1874-9399
DOI	10.1016/j.bbamem.2018.02.015
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Article: Choice of cuvette material can influence spectroscopic leakage and permeability experiments with liposomes

Eriksson, Emma K / Víctor Agmo Hernández

Chemistry and physics of lipids. 2018 Sept., v. 215

2018

Abstract	Liposome solute permeability experiments are widely performed to gain information about lipid membrane characteristics. Spectroscopic methods are often used for this purpose, usually monitoring the leakage of a self-quenching fluorescent dye (e.g., carboxyfluorescein, CF) from the liposomes. Hereby, we investigate the effect of liposome-cuvette interactions, a seldom considered detail, on the results obtained from liposomal permeability experiments. The spontaneous leakage of CF from liposomes with different surface properties and phase states is followed using quartz and polystyrene cuvettes, and the results are compared. It is shown that for most lipid compositions the leakage profiles vary notably between different cuvette materials. Reproducibility of the measurements also varies depending on the cuvettes used, with polystyrene providing with more robust results. To explain these observations, the interaction of liposomes with polystyrene and quartz-like surfaces was characterized with the help of the quartz crystal microbalance with dissipation monitoring (QCM-D). Our results show that, while liposomes seldom interact with polystyrene, quartz-liposome interactions are almost unavoidable and have a large impact on the leakage experiments mainly via two mechanisms: i) the rupturing of liposomes on the cuvette surface causing a fast release of encapsulated CF, and ii) the disruption of adsorbed liposomes caused by magnetic stirring. Depending on their composition, the liposomes interact in different ways with quartz, affecting thus the extent of each proposed mechanism. The experiments demonstrate the importance of considering the cuvette material when planning and conducting spectroscopic experiments with liposomes.
Keywords	encapsulation ; fluorescent dyes ; lipid composition ; lipids ; magnetism ; mixing ; monitoring ; permeability ; polystyrenes ; quartz ; quartz crystal microbalance ; solutes ; spectroscopy
Language	English
Dates of publication	2018-09
Size	p. 63-70.
Publishing place	Elsevier B.V.
Document type	Article
ZDB-ID	213869-4
ISSN	1873-2941 ; 0009-3084
ISSN (online)	1873-2941
ISSN	0009-3084
DOI	10.1016/j.chemphyslip.2018.07.006
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Article: Immune priming using DC- and T cell-targeting gene therapy sensitizes both treated and distant B16 tumors to checkpoint inhibition.

Wenthe, Jessica / Naseri, Sedigheh / Hellström, Ann-Charlotte / Moreno, Rafael / Ullenhag, Gustav / Alemany, Ramon / Lövgren, Tanja / Eriksson, Emma / Loskog, Angelica

Molecular therapy oncolytics

2022 Volume 24, Page(s) 429–442

Abstract: Immune checkpoint inhibitors have revolutionized the treatment of metastatic melanoma, but most tumors show resistance. Resistance is connected to a non-T cell inflamed phenotype partially caused by a lack of functional dendritic cells (DCs) that are ... ...

Abstract	Immune checkpoint inhibitors have revolutionized the treatment of metastatic melanoma, but most tumors show resistance. Resistance is connected to a non-T cell inflamed phenotype partially caused by a lack of functional dendritic cells (DCs) that are crucial for T cell priming. Herein, we investigated whether the adenoviral gene vehicle mLOAd703 carrying both DC- and T cell-activating genes can lead to inflammation in a B16-CD46 model and thereby overcome resistance to checkpoint inhibition therapy. B16-CD46 cells were injected subcutaneously in one or both flanks of immunocompetent C57BL/6J mice. mLOAd703 treatments were given intratumorally alone or in combination with intraperitoneal checkpoint inhibition therapy (anti-PD-1, anti-PD-L1, or anti-TIM-3). Tumor, lymph node, spleen, and serum samples were analyzed for the presence of immune cells and cytokines/chemokines. B16-CD46 tumors were non-inflamed and resistant to checkpoint blockade. In contrast, mLOAd703 treatment led to infiltration of the tumor by CD8
Language	English
Publishing date	2022-01-10
Publishing country	United States
Document type	Journal Article
ISSN	2372-7705
ISSN	2372-7705
DOI	10.1016/j.omto.2022.01.003
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