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Engineered immune cells

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https://www.readbyqxmd.com/read/28723950/high-affinity-anti-tim-3-and-anti-kir-monoclonal-antibodies-cloned-from-healthy-human-individuals
#1
Stefan Ryser, Angeles Estellés, Edgar Tenorio, Lawrence M Kauvar, Mikhail L Gishizky
We report here the cloning of native high affinity anti-TIM-3 and anti-KIR IgG monoclonal antibodies (mAbs) from peripheral blood mononuclear cells (PBMC) of healthy human donors. The cells that express these mAbs are rare, present at a frequency of less than one per 105 memory B-cells. Using our proprietary multiplexed screening and cloning technology CellSpot™ we assessed the presence of memory B-cells reactive to foreign and endogenous disease-associated antigens within the same individual. When comparing the frequencies of antigen-specific memory B-cells analyzed in over 20 screening campaigns, we found a strong correlation of the presence of anti-TIM-3 memory B-cells with memory B-cells expressing mAbs against three disease-associated antigens: (i) bacterial DNABII proteins that are a marker for Gram negative and Gram positive bacterial infections, (ii) hemagglutinin (HA) of influenza virus and (iii) the extracellular domain of anaplastic lymphoma kinase (ALK)...
2017: PloS One
https://www.readbyqxmd.com/read/28722018/a-pro-survival-role-for-the-intracellular-granzyme-b-inhibitor-serpinb9-in-natural-killer-cells-during-poxvirus-infection
#2
Matthew S Mangan, Carolina R Melo-Silva, Jennii Luu, Catherina H Bird, Aulikki Koskinen, Alexandra Rizzitelli, Monica Prakash, Katrina L Scarff, Arno Müllbacher, Matthias Regner, Phillip I Bird
Intracellular serpins are proposed to inactivate proteases released from lysosome-related organelles into the host cell interior, preventing cell death. Serpinb9 opposes the immune cytotoxic protease, granzyme B, and in a number of settings protects cells against granzyme B-mediated cell death. Using a knockout mouse line engineered to express green fluorescent protein under the serpbinb9 promoter, we demonstrate that serpinb9 is vital for host survival during Ectromelia virus infection by maintaining both mature NK cells, and activated CD8(+) T cells...
July 19, 2017: Immunology and Cell Biology
https://www.readbyqxmd.com/read/28721731/self-assembled-injectable-peptide-hydrogels-capable-of-triggering-antitumor-immune-response
#3
Ruirui Xing, Shukun Li, Ning Zhang, Guizhi Shen, Helmuth Möhwald, Xuehai Yan
Self-assembled peptide hydrogels are particularly appealing for drug delivery, tissue engineering, and anti-tumor therapy due to various advantageous features including excellent biocompatibility and biodegradability, defined molecular and higher organized structures and easy availability. However, the poor mechanical and rheological properties of assembled peptide hydrogels cause difficulties in injection, thus limiting further applications. Herein, injectable peptide-based hydrogels with tunable mechanical and rheological properties were obtained by combination with a positively charged poly-peptide (poly-L-lysine, PLL)...
July 19, 2017: Biomacromolecules
https://www.readbyqxmd.com/read/28721573/exposure-to-silver-nanoparticles-affects-viability-and-function-of-natural-killer-cells-mostly-via-the-release-of-ions
#4
Loretta Müller, Selina K Steiner, Laura Rodriguez-Lorenzo, Alke Petri-Fink, Barbara Rothen-Rutishauser, Philipp Latzin
Natural killer (NK) cells play a crucial role in linking innate and adaptive immune responses, especially during viral infections and tumor surveillance. They have two major effector functions: the killing of stressed/abnormal cells and the release of cytokines. Their activity is regulated via inhibitory and activating surface receptors. At the same time that the production and use of engineered nanoparticles is steadily increasing, the risk for exposure to silver nanoparticles (AgNPs) from consumer products or biomedical applications is growing...
July 18, 2017: Cell Biology and Toxicology
https://www.readbyqxmd.com/read/28720569/platelets-as-autonomous-drones-for-hemostatic-and-immune-surveillance
#5
REVIEW
Jackson LiangYao Li, Alexander Zarbock, Andrés Hidalgo
Platelets participate in many important physiological processes, including hemostasis and immunity. However, despite their broad participation in these evolutionarily critical roles, the anucleate platelet is uniquely mammalian. In contrast with the large nucleated equivalents in lower vertebrates, we find that the design template for the evolutionary specialization of platelets shares remarkable similarities with human-engineered unmanned aerial vehicles in terms of overall autonomy, maneuverability, and expendability...
July 18, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28720549/evolutionary-basis-of-a-new-approach-for-the-treatment-of-malignant-brain-tumors-from-mice-to-humans
#6
Pedro R Lowenstein, Maria G Castro
Glioma cells are one of the most aggressive and malignant tumors. Following initial surgery, and radio-chemotherapy they progress rapidly, so that patients' median survival remains under two years. They invade throughout the brain, which makes them difficult to treat, and are universally lethal. Though total resection is always attempted it is not curative. Standard of care in 2016 comprises surgical resection, radiotherapy and chemotherapy (temozolomide). Median survival is currently ~14-20months post-diagnosis though it can be higher in high complexity medical university centers, or during clinical trials...
July 15, 2017: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/28720097/a-versatile-papaya-mosaic-virus-papmv-vaccine-platform-based-on-sortase-mediated-antigen-coupling
#7
Ariane Thérien, Mikaël Bédard, Damien Carignan, Gervais Rioux, Louis Gauthier-Landry, Marie-Ève Laliberté-Gagné, Marilène Bolduc, Pierre Savard, Denis Leclerc
BACKGROUND: Flexuous rod-shaped nanoparticles made of the coat protein (CP) of papaya mosaic virus (PapMV) have been shown to trigger innate immunity through engagement of toll-like receptor 7 (TLR7). PapMV nanoparticles can also serve as a vaccine platform as they can increase the immune response to fused peptide antigens. Although this approach shows great potential, fusion of antigens directly to the CP open reading frame (ORF) is challenging because the fused peptides can alter the structure of the CP and its capacity to self assemble into nanoparticles-a property essential for triggering an efficient immune response to the peptide...
July 18, 2017: Journal of Nanobiotechnology
https://www.readbyqxmd.com/read/28719821/bcg-old-workhorse-new-skills
#8
REVIEW
M Gengenbacher, N E Nieuwenhuizen, She Kaufmann
Bacille Calmette-Guérin (BCG), the only tuberculosis (TB) vaccine in clinical practice, has limitations in efficacy, immunogenicity and safety. Much current TB vaccine research focuses on engineering live mycobacteria to interfere with phagosome biology and host intracellular pathways including apoptosis and autophagy, with candidates such as BCG Δzmp1, BCG ΔureC::hly, BCG::ESX-1(Mmar), Mtb ΔphoP ΔfadD26, Mtb ΔRD1 ΔpanCD and M. smegmatis Δesx-3::esx-3(Mtb) in the development pipeline. Correlates of protection in preclinical studies include increased central memory CD4(+) T cells and recruitment of antigen-specific T cells to the lungs, with mucosal vaccination found to be superior to parenteral vaccination...
July 15, 2017: Current Opinion in Immunology
https://www.readbyqxmd.com/read/28718514/aldehyde-dehydrogenase-1-a1-regulates-energy-metabolism-in-adipocytes-from-different-species
#9
Kefeng Yang, Christopher Adin, Qiwen Shen, Ly James Lee, Lianbo Yu, Paolo Fadda, Arpad Samogyi, Kathleen Ham, Lu Xu, Chen Gilor, Ouliana Ziouzenkova
BACKGROUND: Survival and longevity of xenotransplants depend on immune function and ability to integrate energy metabolism between cells from different species. However, mechanisms for interspecies cross talk in energy metabolism are not well understood. White adipose tissue stores energy and is capable of mobilization and dissipation of energy as heat (thermogenesis) by adipocytes expressing uncoupling protein 1 (Ucp1). Both pathways are under the control of vitamin A metabolizing enzymes...
July 17, 2017: Xenotransplantation
https://www.readbyqxmd.com/read/28717420/comprehensive-toxicity-and-immunogenicity-studies-reveal-minimal-effects-in-mice-following-sustained-dosing-of-extracellular-vesicles-derived-from-hek293t-cells
#10
Xiaohua Zhu, Mohamed Badawi, Steven Pomeroy, Dhruvitkumar S Sutaria, Zhiliang Xie, Alice Baek, Jinmai Jiang, Ola A Elgamal, Xiaokui Mo, Krista La Perle, Jeffrey Chalmers, Thomas D Schmittgen, Mitch A Phelps
Extracellular vesicles (EVs) are under evaluation as therapeutics or as vehicles for drug delivery. Preclinical studies of EVs often use mice or other animal models to assess efficacy and disposition. However, as most EVs under evaluation are derived from human cells, they may elicit immune responses which may contribute to toxicities or enhanced EV clearance. Furthermore, EVs from different cell sources or EVs comprising various cargo may differ with respect to immunogenicity or toxicity. To assess EV-induced immune response and toxicity, we dosed C57BL/6 mice with EVs intravenously and intraperitoneally for 3 weeks...
2017: Journal of Extracellular Vesicles
https://www.readbyqxmd.com/read/28716628/transduction-of-a-neospora-caninum-antigen-gene-into-mammalian-cells-using-a-modified-bombyx-mori-nucleopolyhedrovirus-for-antibody-production
#11
Tatsuya Kato, Kohei Itagaki, Mai Yoshimoto, Rikito Hiramatsu, Hamizah Suhaimi, Tetsuya Kohsaka, Enoch Y Park
Autographa californica multiple nucleopolyhedrovirus (AcMNPV) can easily enter and transduce foreign genes into mammalian cells, but these functions are difficult for Bombyx mori nucleopolyhedrovirus (BmNPV). In this study, we investigated the induction of antibody production in mice immunized with an engineered BmNPV. The GP64 of BmNPV (BmGP64) was replaced with the GP64 of AcMNPV (AcGP64); this construct, designated BmNPVΔbgp/AcGP64, displays AcGP64 on the surface of BmNPV. The Neospora caninum antigen (NcSRS2) expression cassette, consisting of the cytomegalovirus immediate-early promoter and NcSRS2 from N...
July 14, 2017: Journal of Bioscience and Bioengineering
https://www.readbyqxmd.com/read/28714174/immunological-properties-and-protective-efficacy-of-a-single-mycobacterial-antigen-displayed-on-polyhydroxybutyrate-beads
#12
Patricia Rubio-Reyes, Natalie A Parlane, Bryce M Buddle, D Neil Wedlock, Bernd H A Rehm
In 2015, there were an estimated 10.4 million new tuberculosis (TB) cases and 1.4 million deaths worldwide. Bacille Calmette-Guérin (BCG), an attenuated strain of Mycobacterium bovis, is the vaccine available against TB, but it is insufficient for global TB control. This study evaluated the immunogenicity of the Mycobacterium tuberculosis antigen Rv1626 in mice while assessing the effect of co-delivering either Cpe30 (immunostimulatory peptide), CS.T3378-395 (promiscuous T helper epitope) or flagellin (TLR5 agonist) or a combination of all three immunostimulatory agents...
July 17, 2017: Microbial Biotechnology
https://www.readbyqxmd.com/read/28705213/the-therapeutic-landscape-of-hiv-1-via-genome-editing
#13
REVIEW
Alexander Kwarteng, Samuel Terkper Ahuno, Godwin Kwakye-Nuako
Current treatment for HIV-1 largely relies on chemotherapy through the administration of antiretroviral drugs. While the search for anti-HIV-1 vaccine remain elusive, the use of highly active antiretroviral therapies (HAART) have been far-reaching and has changed HIV-1 into a manageable chronic infection. There is compelling evidence, including several side-effects of ARTs, suggesting that eradication of HIV-1 cannot depend solely on antiretrovirals. Gene therapy, an expanding treatment strategy, using RNA interference (RNAi) and programmable nucleases such as meganuclease, zinc finger nuclease (ZFN), transcription activator-like effector nuclease (TALEN), and clustered regularly interspaced short palindromic repeats/CRISPR-associated proteins (CRISPR-Cas9) are transforming the therapeutic landscape of HIV-1...
July 14, 2017: AIDS Research and Therapy
https://www.readbyqxmd.com/read/28705002/preclinical-models-of-pancreatic-ductal-adenocarcinoma
#14
Benjamin D Krempley, Kenneth H Yu
Unlike many other cancers, pancreatic ductal adenocarcinoma (PDAC) has seen only incremental improvement in mortality despite significant advances in our understanding of the underlying biology. A primary obstacle to progress has been our inability to properly model PDAC in a preclinical setting. PDAC is difficult to study because of its genetic heterogeneity, intricate stromal microenvironment, and complex interplay with our immune system. Finding a model that properly accounts for all these criteria remains difficult...
June 2017: Chinese Clinical Oncology
https://www.readbyqxmd.com/read/28701395/preferential-targeting-of-conserved-gag-regions-after-vaccination-with-a-heterologous-dna-prime-modified-vaccinia-ankara-mva-boost-hiv-1-vaccine-regimen
#15
Asli Bauer, Lilli Podola, Philipp Mann, Marco Missanga, Antelmo Haule, Lwitiho Sudi, Charlotta Nilsson, Bahati Kaluwa, Cornelia Lueer, Maria Mwakatima, Patricia J Munseri, Leonard Maboko, Merlin L Robb, Sodsai Tovanabutra, Gustavo Kijak, Mary Marovich, Sheena McCormack, Sarah Joseph, Eligius Lyamuya, Britta Wahren, Eric Sandström, Gunnel Biberfeld, Michael Hoelscher, Muhammad Bakari, Arne Kroidl, Christof Geldmacher
Prime-boost vaccination strategies against HIV-1 often include multiple variants for a given immunogen for better coverage of the extensive viral diversity. To study the immunologic effects of this approach, we characterized breadth, phenotype, function and specificity of Gag-specific T cells induced by a DNA-prime Modified Vaccinia Ankara (MVA)-boost vaccination strategy, which uses mismatched Gag immunogens in the TamoVac 01 phase IIa trial. Healthy Tanzanian volunteers received three injections of the DNA-SMI vaccine encoding for a subtype B and AB-recombinant Gagp37 and two vaccinations with MVA-CMDR encoding subtype A Gagp55 Gag-specific T-cell responses were studied in 42 vaccinees using fresh peripheral blood mononuclear cells...
July 12, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28700955/liver-specific-gene-immunotherapies-resolve-immune-suppressive-ectopic-lymphoid-structures-of-liver-metastases-and-prolong-survival
#16
Tyler J Goodwin, Limei Shen, Mengying Hu, Jingjing Li, Richard Feng, Oleksandra Dorosheva, Rihe Liu, Leaf Huang
The ability to generate potent immunotherapies locally and transiently for the treatment of cancers is a promising strategy to improve efficacy and decrease off-target toxicities. Here, we explored an alternative approach for the delivery of immunotherapeutic agents, in which we deliver the pDNA of an engineered PD-L1 trap and/or CXCL12 trap to the nucleus of liver hepatocytes via a lipid calcium phosphate nanoparticle. This strategy greatly increased the concentrations of immunotherapeutic agents in the local tissue, allowing the therapy to inhibit the accumulation of immune suppressive cells and liver metastasis...
July 6, 2017: Biomaterials
https://www.readbyqxmd.com/read/28699103/expansion-of-pathogen-recognition-specificity-in-plants-using-pattern-recognition-receptors-and-artificially-designed-decoys
#17
REVIEW
Lifan Sun, Jun Qin, Kailun Wang, Jie Zhang
Pathogen/microbe-associated molecular patterns (PAMPs/MAMPs) are recognized by plant pattern recognition receptors (PRRs) localized on the cell surface to activate immune responses. This PAMP-triggered immunity (PTI) confers resistance to a broad range of pathogenic microbes and, therefore, has a great potential for genetically engineering broad-spectrum resistance by transferring PRRs across plant families. Pathogenic effectors secreted by phytopathogens often directly target and inhibit key components of PTI signaling pathways via diverse biochemical mechanisms...
July 10, 2017: Science China. Life Sciences
https://www.readbyqxmd.com/read/28698981/genetically-modified-pigs-as-organ-donors-for-xenotransplantation
#18
REVIEW
Magdalena Hryhorowicz, Joanna Zeyland, Ryszard Słomski, Daniel Lipiński
The growing shortage of available organs is a major problem in transplantology. Thus, new and alternative sources of organs need to be found. One promising solution could be xenotransplantation, i.e., the use of animal cells, tissues and organs. The domestic pig is the optimum donor for such transplants. However, xenogeneic transplantation from pigs to humans involves high immune incompatibility and a complex rejection process. The rapid development of genetic engineering techniques enables genome modifications in pigs that reduce the cross-species immune barrier...
July 11, 2017: Molecular Biotechnology
https://www.readbyqxmd.com/read/28694812/induction-of-innate-immune-memory-by-engineered-nanoparticles-a-hypothesis-that-may-become-true
#19
Paola Italiani, Diana Boraschi
Innate immune memory is the capacity of cells of the innate immune system, such as monocytes and macrophages, to react differently to an inflammatory or infectious challenge if previously exposed to the same or to another agent. Innate immune memory is a protective mechanism, based on epigenetic reprogramming, that ensures effective protection while limiting side effects of tissue damage, by controlling innate/inflammatory responses to repeated stimulations. Engineered nanoparticles (NPs) are novel challenges for our innate immune system, and their ability to induce inflammatory activation, thereby posing health risks, is currently being investigated with controversial results...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28694699/antitumor-hpv-e7-specific-ctl-activity-elicited-by-in-vivo-engineered-exosomes-produced-through-dna-inoculation
#20
Paola Di Bonito, Chiara Chiozzini, Claudia Arenaccio, Simona Anticoli, Francesco Manfredi, Eleonora Olivetta, Flavia Ferrantelli, Emiliana Falcone, Anna Ruggieri, Maurizio Federico
We recently proved that exosomes engineered in vitro to deliver high amounts of HPV E7 upon fusion with the Nef(mut) exosome-anchoring protein elicit an efficient anti-E7 cytotoxic T lymphocyte immune response. However, in view of a potential clinic application of this finding, our exosome-based immunization strategy was faced with possible technical difficulties including industrial manufacturing, cost of production, and storage. To overcome these hurdles, we designed an as yet unproven exosome-based immunization strategy relying on delivery by intramuscular inoculation of a DNA vector expressing Nef(mut) fused with HPV E7...
2017: International Journal of Nanomedicine
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