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Immune engineering

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https://www.readbyqxmd.com/read/28441328/a-gradient-field-pulsed-eddy-current-probe-for-evaluation-of-hidden-material-degradation-in-conductive-structures-based-on-lift-off-invariance
#1
Yong Li, Haoqing Jing, Ilham Mukriz Zainal Abidin, Bei Yan
Coated conductive structures are widely adopted in such engineering fields as aerospace, nuclear energy, etc. The hostile and corrosive environment leaves in-service coated conductive structures vulnerable to Hidden Material Degradation (HMD) occurring under the protection coating. It is highly demanded that HMD can be non-intrusively assessed using non-destructive evaluation techniques. In light of the advantages of Gradient-field Pulsed Eddy Current technique (GPEC) over other non-destructive evaluation methods in corrosion evaluation, in this paper the GPEC probe for quantitative evaluation of HMD is intensively investigated...
April 25, 2017: Sensors
https://www.readbyqxmd.com/read/28439552/direct-observation-of-chiral-currents-and-magnetic-reflection-in-atomic-flux-lattices
#2
Fangzhao Alex An, Eric J Meier, Bryce Gadway
The prospect of studying topological matter with the precision and control of atomic physics has driven the development of many techniques for engineering artificial magnetic fields and spin-orbit interactions. Recently, the idea of introducing nontrivial topology through the use of internal (or external) atomic states as effective "synthetic dimensions" has garnered attraction for its versatility and possible immunity from heating. We engineer tunable gauge fields through the local control of tunneling phases in an effective two-dimensional manifold of discrete atomic momentum states...
April 2017: Science Advances
https://www.readbyqxmd.com/read/28439108/phase-i-trial-of-systemic-administration-of-edmonston-strain-of-measles-virus-genetically-engineered-to-express-the-sodium-iodide-symporter-in-patients-with-recurrent-or-refractory-multiple-myeloma
#3
A Dispenzieri, C Tong, B LaPlant, M Q Lacy, K Laumann, D Dingli, Y Zhou, M J Federspiel, M A Gertz, S Hayman, F Buadi, M O'Connor, V J Lowe, K-W Peng, S J Russell
MV-NIS is an Edmonston-lineage oncolytic measles virus expressing the human sodium-iodide symporter--a means for monitoring by noninvasive imaging of radioiodine. Patients with relapsed, refractory myeloma who had explored all other treatment options were eligible for this Phase I trial. Cohort 1 was treated with intravenous MV-NIS, and Cohort 2 received cyclophosphamide two days prior to MV-NIS. Thirty-two patients were treated. Cohort 1 initially enrolled to 4 dose-levels without reaching MTD and subsequently to 2 higher dose-levels when improved virus manufacture technology made it possible...
April 25, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28437636/chimeric-flock-house-virus-protein-a-with-endoplasmic-reticulum-targeting-domain-enhances-viral-replication-and-virus-like-particle-trans-encapsidation-in-plants
#4
Yiyang Zhou, Christopher M Kearney
Flock House virus (FHV) RNA can be trans-encapsidated, entirely in planta, by tobacco mosaic virus coat protein to form virus-like particles (VLPs). Vaccination with these VLPs leads to strong antigen expression in mice and immune-activation. We hypothesize that creating an additional cellular site for replication and/or trans-encapsidation might significantly improve the final output of trans-encapsidated product. FHV protein A was engineered to target the endoplasmic reticulum (ER) via a heterologous tobacco etch virus ER-targeting domain, and was expressed in cis or in trans relative to the replicating FHV RNA1...
April 21, 2017: Virology
https://www.readbyqxmd.com/read/28437083/dual-plug-and-display-synthetic-assembly-using-orthogonal-reactive-proteins-for-twin-antigen-immunization
#5
Karl Brune, Can Buldun, Yuanyuan Li, Iona Taylor, Florian Brod, Sumi Biswas, Mark Howarth
Engineering modular platforms to control biomolecular architecture can advance both the understanding and manipulation of biological systems. Icosahedral particles uniformly displaying single antigens stimulate potent immune activation and have been successful in various licensed vaccines. However, it remains challenging to display multiple antigens on a single particle, to induce broader immunity protective across strains or even against distinct diseases. Here we design a dually-addressable synthetic nanoparticle, by engineering the multimerizing coiled-coil IMX313 and two orthogonally-reactive split proteins...
April 24, 2017: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/28436934/biopolymers-codelivering-engineered-t-cells-and-sting-agonists-can-eliminate-heterogeneous-tumors
#6
Tyrel T Smith, Howell F Moffett, Sirkka B Stephan, Cary F Opel, Amy G Dumigan, Xiuyun Jiang, Venu G Pillarisetty, Smitha P S Pillai, K Dane Wittrup, Matthias T Stephan
Therapies using T cells that are programmed to express chimeric antigen receptors (CAR T cells) consistently produce positive results in patients with hematologic malignancies. However, CAR T cell treatments are less effective in solid tumors for several reasons. First, lymphocytes do not efficiently target CAR T cells; second, solid tumors create an immunosuppressive microenvironment that inactivates T cell responses; and third, solid cancers are typified by phenotypic diversity and thus include cells that do not express proteins targeted by the engineered receptors, enabling the formation of escape variants that elude CAR T cell targeting...
April 24, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28434891/nanotechnology-based-therapeutic-modality-to-boost-anti-tumor-immunity-and-collapse-tumor-defense
#7
REVIEW
Xiaomeng Hu, Tingting Wu, Yuling Bao, Zhiping Zhang
Cancer is still the leading cause of death. While traditional treatments such as surgery, chemotherapy and radiotherapy play dominating roles, recent breakthroughs in cancer immunotherapy indicate that the influence of immune system on cancer development is virtually beyond our expectation. Manipulating the immune system to fight against cancer has been thriving in recent years. Further understanding of tumor anatomy provides opportunities to put a brake on immunosuppression by overcoming tumor intrinsic resistance or modulating tumor microenvironment...
April 20, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28432128/do-the-microbiota-influence-vaccines-and-protective-immunity-to-pathogens-issues-of-sovereignty-federalism-and-points-testing-in-the-prokaryotic-and-eukaryotic-spaces-of-the-host-microbial-superorganism
#8
Andrew J Macpherson
In contrast to live attenuated vaccines, which are designed to induce immunity through a time-limited bloom in systemic tissues, the microbiota is a persistent feature of body surfaces, especially the intestine. The immune responses to the microbiota are idiosyncratic depending on the niche intimacy of different taxa and generally adapt the host to avoid overgrowth and maintain mutualism rather than to eliminate the organisms of that taxon. Both the microbiota and the host have so much molecular cross talk controlling each other, that the prokaryotic and the eukaryotic spaces of the host-microbial superorganism are federal rather than sovereign...
April 21, 2017: Cold Spring Harbor Perspectives in Biology
https://www.readbyqxmd.com/read/28431919/influence-of-scaffold-design-on-host-immune-and-stem-cell-responses
#9
REVIEW
Ashwin Nair, Liping Tang
The combined culture of isolated stem cells in tissue engineering scaffolds represents a popular strategy for the regeneration of specialized tissues. Despite of improved outcomes in some tissues, this stem cell-seeded tissue engineering strategy has not led to significant tissue regeneration as expected. The lower-than-expected outcome may be caused by overwhelming immune responses to scaffold materials and poor survival of seeded stem cells following implantation. This review is aimed at summarizing the success and failure of this strategy and also shedding some light on new directions to design scaffolds for promoting regenerative responses via autologous stem cells...
April 18, 2017: Seminars in Immunology
https://www.readbyqxmd.com/read/28430023/harnessing-effector-triggered-immunity-for-durable-disease-resistance
#10
Meixiang Zhang, Gitta Coaker
Genetic control of plant diseases has traditionally included the deployment of single immune receptors with nucleotide-binding leucine-rich repeat (NLR) domain architecture. These NLRs recognize corresponding pathogen effector proteins inside plant cells, resulting in effector-triggered immunity (ETI). Although ETI triggers robust resistance, deployment of single NLRs can be rapidly overcome by pathogen populations within a single or a few growing seasons. In order to generate more durable disease resistance against devastating plant pathogens, a multi-tiered strategy that incorporates stacked NLRs combined with other sources of disease resistance is necessary...
April 21, 2017: Phytopathology
https://www.readbyqxmd.com/read/28428503/-cancer-immunotherapy-utilizing-t-cell-receptor-gene-engineering
#11
Hiroaki Ikeda
Immune-checkpoint inhibitors have shown their efficacy in the treatment of patients with many kinds of progressive/relapsed cancers. However, the efficacy remains as 10-40%of the patients in most type of cancers, suggesting that the development of new therapy for patients resistant to the therapy is an urgent unmet need. Adoptive therapy with tumor-specific T cells is a promising therapy that can be effective in patients who are not benefited from the immune-checkpoint inhibitors. The T cell therapy with genetic engineering in T cell receptor(TCR)is expected to be a universal therapy because this therapy can be applicable for patients with many kinds of cancers...
April 2017: Gan to Kagaku Ryoho. Cancer & Chemotherapy
https://www.readbyqxmd.com/read/28428135/the-immunotoxicological-pattern-of-subchronic-and-chronic-benzene-exposure-in-rats
#12
Alexander V Karaulov, Irina V Mikhaylova, Alexander I Smolyagin, Viktor M Boev, Alexandra Kalogeraki, Aristides M Tsatsakis, Ayse Basak Engin
Exposure to benzene and its inevitable metabolites can result in deleterious effects on human health, including lymphocytopenia, hematotoxicity and cancer. However, the duration of exposure might alter the effects including immune consequences. The aim of this study was to determine whether benzene could modulate lymphocyte proliferation induced by the T cell mitogen concanavalin A, in rats, at different exposure durations. 386 Wistar rats were assigned into control and treatment groups which was subdivided into groups for 45, 90 and 135days for 0,6mL/kg of drinking water mixed benzene treatment...
April 17, 2017: Toxicology Letters
https://www.readbyqxmd.com/read/28427157/the-anti-tumor-efficacy-of-3c23k-a-glyco-engineered-humanized-anti-misrii-antibody-in-an-ovarian-cancer-model-is-mainly-mediated-by-engagement-of-immune-effector-cells
#13
Pauline Estupina, Alexandre Fontayne, Jean-Marc Barret, Nathalie Kersual, Olivier Dubreuil, Marion Le Blay, Alexandre Pichard, Marta Jarlier, Martine Pugnière, Maëva Chauvin, Thierry Chardès, Jean-Pierre Pouget, Emmanuel Deshayes, Alexis Rossignol, Toufik Abache, Christophe de Romeuf, Aurélie Terrier, Lucie Verhaeghe, Christine Gaucher, Jean-François Prost, André Pèlegrin, Isabelle Navarro-Teulon
Ovarian cancer is the leading cause of death in women with gynecological cancers and despite recent advances, new and more efficient therapies are crucially needed. Müllerian Inhibiting Substance type II Receptor (MISRII, also named AMHRII) is expressed in most ovarian cancer subtypes and is a novel potential target for ovarian cancer immunotherapy. We previously developed and tested 12G4, the first murine monoclonal antibody (MAb) against human MISRII. Here, we report the humanization, affinity maturation and glyco-engineering steps of 12G4 to generate the Fc-optimized 3C23K MAb, and the evaluation of its in vivo anti-tumor activity...
February 24, 2017: Oncotarget
https://www.readbyqxmd.com/read/28426273/preclinical-development-of-bcg-hiva-2auxo-int-harboring-an-integrative-expression-vector-for-a-hiv-tb-pediatric-vaccine-enhancement-of-stability-and-specific-hiv-1-t-cell-immunity
#14
Aakash Mahant, Narcís Saubi, Yoshiki Eto, Núria Guitart, Josep M ª Gatell, Tomáš Hanke, Joan Joseph
One of the critical issues that should be addressed in the development of a BCG-based HIV vaccine is genetic plasmid stability. Therefore, to address this issue we have considered using integrative vectors and the auxotrophic mutant of BCG complemented with a plasmid carrying a wild-type complementing gene. In this study, we have constructed an integrative E. coli-mycobacterial shuttle plasmid, p2auxo.HIVA(int), expressing the HIV-1 clade A immunogen HIVA. This shuttle vector employs an antibiotic resistance-free mechanism for plasmid selection and maintenance...
April 20, 2017: Human Vaccines & Immunotherapeutics
https://www.readbyqxmd.com/read/28421694/molecular-engineering-and-plant-expression-of-an-immunoglobulin-heavy-chain-scaffold-for-delivery-of-a-dengue-vaccine-candidate
#15
Mi-Young Kim, Craig Van Dolleweerd, Alastair Copland, Matthew John Paul, Sven Hofmann, Gina R Webster, Emily Julik, Ivonne Ceballos-Olvera, Jorge Reyes-Del Valle, Moon-Sik Yang, Yong-Suk Jang, Rajko Reljic, Julian K Ma
In order to enhance vaccine uptake by the immune cells in vivo, molecular engineering approach was employed to construct a Polymeric Immunoglobulin G Scaffold (PIGS) that incorporates multiple copies of an antigen and targets the Fc gamma receptors on antigen-presenting cells. These self-adjuvanting immunogens were tested in the context of dengue infection, for which there is currently no globally licensed vaccine yet. Thus, the consensus domain III sequence (cEDIII) of dengue glycoprotein E was incorporated into PIGS and expressed in both tobacco plants and Chinese Ovary Hamster cells...
April 19, 2017: Plant Biotechnology Journal
https://www.readbyqxmd.com/read/28421069/engineering-chimeric-antigen-receptor-t-cells-for-racing-in-solid-tumors-don-t-forget-the-fuel
#16
REVIEW
Melita Irving, Romain Vuillefroy de Silly, Kirsten Scholten, Nahzli Dilek, George Coukos
T-cells play a critical role in tumor immunity. Indeed, the presence of tumor-infiltrating lymphocytes is a predictor of favorable patient prognosis for many indications and is a requirement for responsiveness to immune checkpoint blockade therapy targeting programmed cell death 1. For tumors lacking immune infiltrate, or for which antigen processing and/or presentation has been downregulated, a promising immunotherapeutic approach is chimeric antigen receptor (CAR) T-cell therapy. CARs are hybrid receptors that link the tumor antigen specificity and affinity of an antibody-derived single-chain variable fragment with signaling endodomains associated with T-cell activation...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28420742/synergistic-internal-ribosome-entry-site-microrna-based-approach-for-flavivirus-attenuation-and-live-vaccine-development
#17
Konstantin A Tsetsarkin, Guangping Liu, Evgeniya Volkova, Alexander G Pletnev
The recent emergence of Zika virus underscores the need for new strategies for a rapid development of safe flavivirus vaccines. Using another flavivirus (Langat virus [LGTV]) that belongs to the group of tick-borne flaviviruses as a model, we describe a dual strategy for virus attenuation which synergistically accesses the specificity of microRNA (miRNA) genome targeting and the effectiveness of internal ribosome entry site (IRES) insertion. To increase the stability and immunogenicity of bicistronic LGTVs, we developed a novel approach in which the capsid (C) protein gene was relocated into the 3' noncoding region (NCR) and expressed under translational control from an IRES...
April 18, 2017: MBio
https://www.readbyqxmd.com/read/28419211/the-inhibitory-g-protein-%C3%AE-subunit-g%C3%AE-z-promotes-type-1-diabetes-like-pathophysiology-in-nod-mice
#18
Rachel J Fenske, Mark T Cadena, Quincy E Harenda, Haley N Wienkes, Kathryn Carbajal, Michael D Schaid, Erin Laundre, Allison L Brill, Nathan A Truchan, Harpreet Brar, Jaclyn Wisinski, Jinjin Cai, Timothy E Graham, Feyza Engin, Michelle E Kimple
The alpha subunit of the heterotrimeric Gz protein, Gαz, promotes beta-cell death and inhibits beta-cell replication when pancreatic islets are challenged by stressors. Thus, we hypothesized that loss of Gαz protein would preserve functional beta-cell mass in the non-obese diabetic (NOD) model, protecting from overt diabetes. We saw that protection from diabetes was robust and durable up to 35 weeks of age in Gαz knockout mice. By 17 weeks of age, Gαz-null NOD mice had significantly higher diabetes-free survival than wild-type littermates...
April 14, 2017: Endocrinology
https://www.readbyqxmd.com/read/28417936/oncolytic-alphaviruses-in-cancer-immunotherapy
#19
REVIEW
Kenneth Lundstrom
Oncolytic viruses show specific targeting and killing of tumor cells and therefore provide attractive assets for cancer immunotherapy. In parallel to oncolytic viral vectors based on adenoviruses and herpes simplex viruses, oncolytic RNA viruses and particularly alphaviruses have been evaluated as delivery vehicles. Immunization studies in experimental rodent models for various cancers including glioblastoma, hematologic, hepatocellular, colon, cervix, and lung cancer as well as melanoma have been conducted with naturally occurring oncolytic alphavirus strains such as M1 and Sindbis AR339...
April 12, 2017: Vaccines
https://www.readbyqxmd.com/read/28416651/aav-mediated-expression-of-anti-tau-scfvs-decreases-tau-accumulation-in-a-mouse-model-of-tauopathy
#20
Christina Ising, Gilbert Gallardo, Cheryl E G Leyns, Connie H Wong, Floy Stewart, Lauren J Koscal, Joseph Roh, Grace O Robinson, Javier Remolina Serrano, David M Holtzman
Tauopathies are characterized by the progressive accumulation of hyperphosphorylated, aggregated forms of tau. Our laboratory has previously demonstrated that passive immunization with an anti-tau antibody, HJ8.5, decreased accumulation of pathological tau in a human P301S tau-expressing transgenic (P301S-tg) mouse model of frontotemporal dementia/tauopathy. To investigate whether the Fc domain of HJ8.5 is required for the therapeutic effect, we engineered single-chain variable fragments (scFvs) derived from HJ8...
April 17, 2017: Journal of Experimental Medicine
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