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Engineered immune cells

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https://www.readbyqxmd.com/read/28098169/ifn-%C3%AE-regulates-human-dental-pulp-stem-cells-behavior-via-nf-%C3%AE%C2%BAb-and-mapk-signaling
#1
Xinyao He, Wenkai Jiang, Zhirong Luo, Tiejun Qu, Zhihua Wang, Ningning Liu, Yaqing Zhang, Paul R Cooper, Wenxi He
During caries, dental pulp expresses a range of pro-inflammatory cytokines in response to the infectious challenge. Interferon gamma (IFN-γ) is a dimerized soluble cytokine, which is critical for immune responses. Previous study has demonstrated that IFN-γ at relative high concentration (100 ng/mL) treatment improved the impaired dentinogenic and immunosuppressive regulatory functions of disease-derived dental pulp stem cells (DPSCs). However, little is known about the regulatory effects of IFN-γ at relative low concentration on healthy DPSC behavior (including proliferation, migration, and multiple-potential differentiation)...
January 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28096534/novel-therapeutic-approach-to-improve-hematopoiesis-in-low-risk-mds-by-targeting-mdscs-with-the-fc-engineered-cd33-antibody-bi-836858
#2
E A Eksioglu, X Chen, K-H Heider, B Rueter, K L McGraw, A A Basiorka, M Wei, A Burnette, P Cheng, J Lancet, R Komrokji, J Djeu, A List, S Wei
We recently reported that the accumulation of myeloid-derived suppressor cells (MDSC), defined as CD33(+)HLA-DR(-)Lin(-), plays a direct role in the pathogenesis of myelodysplastic syndrome (MDS). In particular, CD33 is strongly expressed in MDSC isolated from patients with MDS where it plays an important role in MDSC-mediated hematopoietic suppressive function through its activation by S100A9. Therefore, we tested whether blocking this interaction with a fully human, Fc-engineered monoclonal antibody against CD33 (BI 836858) suppresses CD33-mediated signal transduction and improves the bone marrow microenvironment in MDS...
January 18, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28092363/mouse-models-of-uv-induced-melanoma-genetics-pathology-and-clinical-relevance
#3
Chi-Ping Day, Rachel Marchalik, Glenn Merlino, Helen Michael
Melanocytes, a neural crest cell derivative, produce pigment to protect keratinocytes from ultraviolet radiation (UVR). Although melanocytic lesions such as nevi and cutaneous malignant melanomas are known to be associated with sun exposure, the role of UVR in oncogenesis is complex and has yet to be clearly elucidated. UVR appears to have a direct mutational role in inducing or promoting melanoma formation as well as an indirect role through microenvironmental changes. Recent advances in the modeling of human melanoma in animals have built platforms upon which prospective studies can begin to investigate these questions...
January 16, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/28087528/engineering-mycobacteria-for-the-production-of-self-assembling-biopolyesters-displaying-mycobacterial-antigens-for-use-as-tuberculosis-vaccine
#4
Jason W Lee, Natalie A Parlane, Bernd H A Rehm, Bryce M Buddle, Axel Heiser
: Tuberculosis (TB) is a disease caused by Mycobacterium tuberculosis or Mycobacterium bovis and still remains one of the world's biggest global health burdens. Recently, engineered polyhydroxyalkanoate (PHA) biobeads produced in both E. coli and Lactococcus lactis displaying mycobacterial antigens were found to induce significant cell mediated immune responses in mice. We observed that such PHA beads contained host cell proteins as impurities which we hypothesized to have the potential to induce immunity...
January 13, 2017: Applied and Environmental Microbiology
https://www.readbyqxmd.com/read/28077318/alcohol-microbiome-life-style-influence-alcohol-and-non-alcoholic-organ-damage
#5
REVIEW
Manuela G Neuman, Samuel W French, Samir Zakhari, Stefen Malnick, Helmut K Seitz, Lawrence B Cohen, Mikko Salaspuro, Andreea Voinea Griffin, Andrei Barasch, Irina A Kirpich, Paul G Thomes, Laura W Schrum, Terrence M Donohue, Kusum Kharbanda, Marcus Cruz, Mihai Opris
This paper is based upon the "8th Charles Lieber's Satellite Symposium" organized by Manuela G. Neuman at the Research Society on Alcoholism Annual Meeting, onJune 25, 2016 at New Orleans, Louisiana, USA. The integrative symposium investigated different aspects of alcohol-induced liver disease (ALD) as well as non-alcohol-induced liver disease (NAFLD) and possible repair. We revealedthe basic aspects of alcohol metabolism that may be responsible for the development of liver diseaseas well as the factors that determine the amount, frequency and which type of alcohol misuse leads to liver and gastrointestinal diseases...
January 7, 2017: Experimental and Molecular Pathology
https://www.readbyqxmd.com/read/28076778/axl-mediates-zika-virus-entry-in-human-glial-cells-and-modulates-innate-immune-responses
#6
Laurent Meertens, Athena Labeau, Ophelie Dejarnac, Sara Cipriani, Laura Sinigaglia, Lucie Bonnet-Madin, Tifenn Le Charpentier, Mohamed Lamine Hafirassou, Alessia Zamborlini, Van-Mai Cao-Lormeau, Muriel Coulpier, Dorothée Missé, Nolwenn Jouvenet, Ray Tabibiazar, Pierre Gressens, Olivier Schwartz, Ali Amara
ZIKA virus (ZIKV) is an emerging pathogen responsible for neurological disorders and congenital microcephaly. However, the molecular basis for ZIKV neurotropism remains poorly understood. Here, we show that Axl is expressed in human microglia and astrocytes in the developing brain and that it mediates ZIKV infection of glial cells. Axl-mediated ZIKV entry requires the Axl ligand Gas6, which bridges ZIKV particles to glial cells. Following binding, ZIKV is internalized through clathrin-mediated endocytosis and traffics to Rab5+ endosomes to establish productive infection...
January 10, 2017: Cell Reports
https://www.readbyqxmd.com/read/28075126/cell-conditioned-protein-coronas-on-engineered-particles-influence-immune-responses
#7
Qiong Dai, Junling Guo, Yan Yan, Ching-Seng Ang, Nadja Bertleff-Zieschang, Frank Caruso
A protein corona, which forms on engineered particles as soon as they are introduced into biological environments, is known to provide particles with a "biological identity". Protein coronas derived from various biological environments have been demonstrated to alter the cell internalization mechanism, to diminish targeting ability and to induce nanoparticle aggregation. So far, most of these studies have challenged engineered particles with a static biological environment. However, the extracellular environment is highly dynamic due to the process termed "cell-conditioning", in which cells deplete and secrete biomolecules...
January 11, 2017: Biomacromolecules
https://www.readbyqxmd.com/read/28069500/solution-blow-spinning-fibres-new-immunologically-inert-substrates-for-the-analysis-of-cell-adhesion-and-motility
#8
Rafaella T Paschoalin, Bruna Traldi, Gülcan Aydin, Juliano E Oliveira, Stephan Rütten, Luiz H C Mattoso, Martin Zenke, Antonio Sechi
The control of cell behaviour through material geometry is appealing as it avoids the requirement for complex chemical surface modifications. Significant advances in new technologies have been made to the development of polymeric biomaterials with controlled geometry and physico-chemical properties. Solution blow spinning technique has the advantage of ease of use allowing the production of nano or microfibres and the direct fibre deposition on any surface in situ. Yet, in spite of these advantages, very little is known about the influence of such fibres on biological functions such as immune response and cell migration...
January 6, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/28069025/interaction-of-biomedical-nanoparticles-with-the-pulmonary-immune-system
#9
REVIEW
Fabian Blank, Kleanthis Fytianos, Emilie Seydoux, Laura Rodriguez-Lorenzo, Alke Petri-Fink, Christophe von Garnier, Barbara Rothen-Rutishauser
Engineered nanoparticles (NPs) offer site-specific delivery, deposition and cellular uptake due to their unique physicochemical properties and were shown to modulate immune responses. The respiratory tract with its vast surface area is an attractive target organ for innovative immunomodulatory therapeutic applications by pulmonary administration of such NPs, enabling interactions with resident antigen-presenting cells (APCs), such as dendritic cells and macrophages. Depending on the respiratory tract compartment, e...
January 9, 2017: Journal of Nanobiotechnology
https://www.readbyqxmd.com/read/28068879/electrospun-template-architecture-and-composition-regulate-neutrophil-netosis-in-vitro-and-in-vivo
#10
Allison E Fetz, Indira Neeli, Isaac A Rodriguez, Marko Z Radic, Gary Bowlin
Mounting evidence indicates that neutrophils, first responders to an implanted biomaterial, prime the microenvironment for recruited immune cells by secreting factors and releasing neutrophil extracellular traps (NETs) through NETosis. In this study, we investigated the role of electrospun template architecture and composition in regulating NETosis. Electrospun polydioxanone (PDO), collagen type I (COL), and blended PDO-COL templates (PC) were fabricated with small (0.25-0.35µm) and large (1.0-2.00µm) diameter fibers...
January 9, 2017: Tissue Engineering. Part A
https://www.readbyqxmd.com/read/28067810/bioactivity-of-natural-and-engineered-antimicrobial-peptides-from-venom-of-the-scorpions-urodacus-yaschenkoi-and-u-manicatus
#11
Karen Luna-Ramirez, Miray Tonk, Mohammad Rahnamaeian, Andreas Vilcinskas
The spread of multidrug-resistant human pathogens has drawn attention towards antimicrobial peptides (AMPs), which are major players in the innate immune systems of many organisms, including vertebrates, invertebrates, plants and microbes. Scorpion venom is an abundant source of novel and potent AMPs. Here, we investigated natural and engineered AMPs from the scorpions Urodacus yaschenkoi and U. manicatus to determine their antimicrobial spectra as well as their hemolytic/cytotoxic activity. None of the AMPs were active against fungi, but many of them were active at low concentrations (0...
January 6, 2017: Toxins
https://www.readbyqxmd.com/read/28064157/fviii-specific-human-chimeric-antigen-receptor-car-t-regulatory-cells-suppress-t-and-b-cell-responses-to-fviii
#12
Jeongheon Yoon, Anja Schmidt, Ai-Hong Zhang, Christoph Königs, Yong Chan Kim, David W Scott
Replacement therapy with factor VIII (FVIII) is used in hemophilia A patients for treatment of bleeding episodes or for prophylaxis. A common and serious problem with this therapy is the patient's immune response to FVIII, due to a lack of tolerance, leading to the formation of inhibitory antibodies. Development of tolerogenic therapies, other than standard ITI, is an unmet goal. We previously generated engineered antigen- specific regulatory T cells (Tregs), created by transduction of a recombinant T cell receptor (TCR) isolated from a hemophilia A subject's T cell clone...
November 15, 2016: Blood
https://www.readbyqxmd.com/read/28063980/plant-viral-nanoparticles-based-her2-vaccine-immune-response-influenced-by-differential-transport-localization-and-cellular-interactions-of-particulate-carriers
#13
Sourabh Shukla, Jay T Myers, Sarah E Woods, Xingjian Gong, Anna E Czapar, Ulrich Commandeur, Alex Y Huang, Alan D Levine, Nicole F Steinmetz
Cancer vaccines are designed to elicit an endogenous adaptive immune response that can successfully recognize and eliminate residual or recurring tumors. Such approaches can potentially overcome shortcomings of passive immunotherapies by generating long-lived therapeutic effects and immune memory while limiting systemic toxicities. A critical determinant of vaccine efficacy is efficient transport and delivery of tumor-associated antigens to professional antigen presenting cells (APCs). Plant viral nanoparticles (VNPs) with natural tropism for APCs and a high payload carrying capacity may be particularly effective vaccine carriers...
December 27, 2016: Biomaterials
https://www.readbyqxmd.com/read/28061981/talimogene-laherparepvec-t-vec-for-the-treatment-of-melanoma-and-other-cancers
#14
REVIEW
Claud Grigg, Zoë Blake, Robyn Gartrell, Adrian Sacher, Bret Taback, Yvonne Saenger
Talimogene laherparepvec (T-Vec) is the first live virus to be approved by the US Food and Drug Administration for the treatment of cancer. This engineered version of herpes simplex virus type 1 (HSV-1) is the product of decades of preclinical work aimed at identifying and modifying aspects of the viral genome involved in virulence and immunogenicity. T-Vec preferentially infects and lyses tumor cells and, in some cases, induces a systemic immune response against the tumor. These properties have translated into significant and durable clinical responses, particularly in advanced melanoma...
December 2016: Seminars in Oncology
https://www.readbyqxmd.com/read/28060516/glycosylation-characterization-of-an-influenza-h5n7-hemagglutinin-series-with-engineered-glycosylation-patterns-implications-for-structure-function-relationships
#15
Lisa M Parsons, Yanming An, Robert P de Vries, Cornelis A M de Haan, John F Cipollo
The glycosylation patterns of four recombinant H5 hemagglutinins (HAs) derived from A/Mallard/Denmark/64650/03 (H5N7) have been characterized. The proteins were expressed in (i) HEK293T cells to produce complex glycoforms, (ii) HEK293T cells treated with Vibrio cholera neuraminidase to provide asialo-complex glycoforms, (iii) HEK293S GnTI(-) cells with predominantly the canonical Man5GlcNAc2 glycoform, and (iv) Drosophila S2 insect cells producing primarily paucimannose glycoforms. Previously, these HAs were used to investigate the effect of different glycosylation states on the immune responses in chicken and mouse systems...
December 5, 2016: Journal of Proteome Research
https://www.readbyqxmd.com/read/28052622/novel-targets-for-hepatitis-b-virus-therapy
#16
REVIEW
Barbara Testoni, David Durantel, Fabien Zoulim
Treatment with either pegylated interferon-alpha (pegIFN-α) or last generation nucleos(t)ide analogues (NAs) successfully leads to serum viral load suppression in most chronically infected hepatitis B (CHB) patients, but HBsAg loss is only achieved in 10% of the cases after a 5-year follow-up. Thus, therapy must be administered long-term and it will not completely eliminate infection because of the persistent hepatitis B virus (HBV) minichromosome in infected cells, and cannot completely abolish the risk of developing severe sequelae such as cirrhosis and hepatocellular carcinoma...
January 2017: Liver International: Official Journal of the International Association for the Study of the Liver
https://www.readbyqxmd.com/read/28051268/immunoregulatory-effect-of-neuronal-like-cells-in-inducting-differentiation-of-bone-marrow-mesenchymal-stem-cells
#17
J Xu, H Lu, Z-N Miao, W-J Wu, Y -Z Jiang, F Ge, W-F Fang, A-H Zhu, G Chen, J-H Zhou, Y-Z Lu, Z-F Tang, Y Wang
OBJECTIVE: To evaluate the immune activity of bone marrow mesenchymal stem cells (BMSCs), and explore the biological characteristics and capabilities of BMSCs and the potential to be differentiated into neuronal cells in vitro. MATERIALS AND METHODS: The BMSCs were isolated and proliferated in vitro to generate the xenogeneic mixed lymphocyte reaction. Moreover, peripheral BMSCs (pBMSCs) were added according to different ratios, which methods were stated as follows: 1: Dulbecco's Modified Eagle Medium (DMEM) + 10% Fetal Bovine Serum (FBS) + 1 μmol/L all-trans-retinoic acid (ATRA) + 20 μg/L basic fibroblast growth factor (bFGF) + 20 μg/L epidermal growth factor (EGF); 2: DMEM + 2% dimethyl sulfoxide (DMSO) + 100 μmol/L butylated hydroxyanisole (BHA)...
December 2016: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/28049494/adjuvant-effects-of-a-sequence-engineered-mrna-vaccine-translational-profiling-demonstrates-similar-human-and-murine-innate-response
#18
Darin K Edwards, Edith Jasny, Heesik Yoon, Nigel Horscroft, Brian Schanen, Tanya Geter, Mariola Fotin-Mleczek, Benjamin Petsch, Vaughan Wittman
BACKGROUND: Prophylactic and therapeutic vaccines often depend upon a strong activation of the innate immune system to drive a potent adaptive immune response, often mediated by a strong adjuvant. For a number of adjuvants immunological readouts may not be consistent across species. METHODS: In this study, we evaluated the innate immunostimulatory potential of mRNA vaccines in both humans and mice, using a novel mRNA-based vaccine encoding influenza A hemagglutinin of the pandemic strain H1N1pdm09 as a model...
January 3, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28049484/a-new-insight-in-chimeric-antigen-receptor-engineered-t-cells-for-cancer-immunotherapy
#19
REVIEW
Erhao Zhang, Hanmei Xu
Adoptive cell therapy using chimeric antigen receptor (CAR)-engineered T cells has emerged as a very promising approach to combating cancer. Despite its ability to eliminate tumors shown in some clinical trials, CAR-T cell therapy involves some significant safety challenges, such as cytokine release syndrome (CRS) and "on-target, off-tumor" toxicity, which is related to poor control of the dose, location, and timing of T cell activity. In the past few years, some strategies to avoid the side effects of CAR-T cell therapy have been reported, including suicide gene, inhibitory CAR, dual-antigen receptor, and the use of exogenous molecules as switches to control the CAR-T cell functions...
January 3, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28043149/mesenchymal-stromal-cells-producing-tnf%C3%AE-lack-inhibitory-effect-against-a375-experimental-lung-metastasis
#20
S Tyciakova, M Matuskova, R Bohovic, L Kucerova
Cell-based anticancer therapy using mesenchymal stromal cells (MSCs) engineered to express therapeutic genes has a potential to target the cancer cells in vivo. Metastatic dissemination of melanoma remains a serious problem in the treatment. In our previous work we used MSCs overexpressing gene for tumor necrosis factor α (TNFα; MSCs/TNFα), and we achieved inhibition of melanoma xenograft growth when engineered MCSs/TNFα were coinjected with tumor cells subcutaneously. The TNFα as a pleiotropic cytokine induces apoptosis of tumor cells, creates "tumor resistant" microenvironment, enhances immune response and can have tumor destructive capacity in selected tumor types, especially in tumors of mesodermal origin...
January 3, 2017: Neoplasma
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