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Immune engineering

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https://www.readbyqxmd.com/read/28820071/antibody-fragments-as-potential-biopharmaceuticals-for-cancer-therapy-success-and-limitations
#1
Roman V Kholodenko, Daniel V Kalinovsky, Igor I Doronin, Eugene D Ponomarev, Irina V Kholodenko
Monoclonal antibodies (mAbs) are an important class of therapeutic agents approved for the therapy of many types of malignancies. However, in certain cases applications of conventional mAbs have several limitations in anticancer immunotherapy. These limitations include insufficient efficacy and adverse effects. The antigen-binding fragments of antibodies have a considerable potential to overcome the disadvantages of conventional mAbs, such as poor penetration into solid tumors and Fc-mediated bystander activation of the immune system...
August 17, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28818634/mining-na%C3%A3-ve-rabbit-antibody-repertoires-by-phage-display-for-monoclonal-antibodies-of-therapeutic-utility
#2
Haiyong Peng, Thomas Nerreter, Jing Chang, Junpeng Qi, Xiuling Li, Pabalu Karunadharma, Gustavo Martinez, Mohammad Fallahi, Jo Soden, Jim Freeth, Roger R Beerli, Ulf Grawunder, Michael Hudecek, Christoph Rader
Owing to their high affinities and specificities, rabbit monoclonal antibodies (mAbs) have demonstrated value and potential primarily as basic research and diagnostic reagents, but in some cases also as therapeutics. To accelerate access to rabbit mAbs bypassing immunization, we generated a large naïve rabbit antibody repertoire represented by a phage display library encompassing >10 billion independent antibodies in chimeric rabbit/human Fab format and validated it by next-generation sequencing. Panels of rabbit mAbs selected from this library against two emerging cancer targets, ROR1 and ROR2, revealed high diversity, affinity, and specificity...
August 14, 2017: Journal of Molecular Biology
https://www.readbyqxmd.com/read/28816564/cytotoxicity-screening-and-cytokine-profiling-of-nineteen-nanomaterials-enables-hazard-ranking-and-grouping-based-on-inflammogenic-potential
#3
Kunal Bhattacharya, Gözde Kiliç, Pedro M Costa, Bengt Fadeel
Engineered nanomaterials (ENMs) are being produced for an increasing number of applications. Therefore, it is important to assess and categorize ENMs on the basis of their hazard potential. The immune system is the foremost defence against foreign bodies. Here we performed cytokine profiling of a panel of nineteen representative ENMs procured from the Joint Research Centre (JRC) and commercial sources. Physicochemical characterization was performed using dynamic light scattering. The ENMs were all shown to be endotoxin content free...
August 17, 2017: Nanotoxicology
https://www.readbyqxmd.com/read/28816104/the-immune-response-to-allogeneic-differentiated-mesenchymal-stem-cells-in-the-context-of-bone-tissue-engineering
#4
Caoimhe H Kiernan, Eppo B Wolvius, Pieter A J Brama, Eric Farrell
The use of allogeneic differentiated mesenchymal stem cells (MSCs) to mediate bone formation may be a potential alternative to the current gold standards of bone repair. While it is known that undifferentiated MSCs are immunomodulatory and weakly immunogenic, the host immune reaction to differentiated MSCs is less known. Implantation of allogeneic osteogenic or chondrogenically differentiated MSC pellets may be promising routes to induce bone repair via the processes of intramembranous and endochondral ossification...
August 17, 2017: Tissue Engineering. Part B, Reviews
https://www.readbyqxmd.com/read/28814602/carbon-nanoparticles-inhibit-the-antimicrobial-activities-of-the-human-cathelicidin-ll-37-through-structural-alteration
#5
Fern Findlay, Jan Pohl, Pavel Svoboda, Priyanka Shakamuri, Kevin McLean, Neil F Inglis, Lorna Proudfoot, Peter G Barlow
Host defense peptides, also known as antimicrobial peptides, are key elements of innate host defense. One host defense peptide with well-characterized antimicrobial activity is the human cathelicidin, LL-37. LL-37 has been shown to be upregulated at sites of infection and inflammation and is regarded as one of the primary innate defense molecules against bacterial and viral infection. Human exposure to combustion-derived or engineered nanoparticles is of increasing concern, and the implications of nanomaterial exposure on the human immune response is poorly understood...
August 16, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28811974/ex-vivo-assessment-of-drug-response-on-breast-cancer-primary-tissue-with-preserved-microenvironments
#6
Manuele G Muraro, Simone Muenst, Valentina Mele, Luca Quagliata, Giandomenica Iezzi, Alexandar Tzankov, Walter P Weber, Giulio C Spagnoli, Savas D Soysal
Interaction between cancerous, non-transformed cells, and non-cellular components within the tumor microenvironment plays a key role in response to treatment. However, short-term culture or xenotransplantation of cancer specimens in immunodeficient animals results in dramatic modifications of the tumor microenvironment, thus preventing reliable assessment of compounds or biologicals of potential therapeutic relevance. We used a perfusion-based bioreactor developed for tissue engineering purposes to successfully maintain the tumor microenvironment of freshly excised breast cancer tissue obtained from 27 breast cancer patients and used this platform to test the therapeutic effect of antiestrogens as well as checkpoint-inhibitors on the cancer cells...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28807998/immunogenicity-and-structures-of-a-rationally-designed-prefusion-mers-cov-spike-antigen
#7
Jesper Pallesen, Nianshuang Wang, Kizzmekia S Corbett, Daniel Wrapp, Robert N Kirchdoerfer, Hannah L Turner, Christopher A Cottrell, Michelle M Becker, Lingshu Wang, Wei Shi, Wing-Pui Kong, Erica L Andres, Arminja N Kettenbach, Mark R Denison, James D Chappell, Barney S Graham, Andrew B Ward, Jason S McLellan
Middle East respiratory syndrome coronavirus (MERS-CoV) is a lineage C betacoronavirus that since its emergence in 2012 has caused outbreaks in human populations with case-fatality rates of ∼36%. As in other coronaviruses, the spike (S) glycoprotein of MERS-CoV mediates receptor recognition and membrane fusion and is the primary target of the humoral immune response during infection. Here we use structure-based design to develop a generalizable strategy for retaining coronavirus S proteins in the antigenically optimal prefusion conformation and demonstrate that our engineered immunogen is able to elicit high neutralizing antibody titers against MERS-CoV...
August 14, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28806522/development-of-a-recombinant-multifunctional-biomacromolecule-for-targeted-gene-transfer-to-prostate-cancer-cells
#8
Arash Hatefi, Zahra Karjoo, Alireza Nomani
The objective of this study was to genetically engineer a fully functional single chain fusion peptide composed of motifs from diverse biological and synthetic origins that can perform multiple tasks including DNA condensation, cell targeting, cell transfection, particle shielding from immune system and effective gene transfer to prostate tumors. To achieve the objective, a single chain biomacromolecule (vector) consisted of four repetative units of histone H2A peptide, fusogenic peptide GALA, short elastin-like peptide and PC-3 cell targeting peptide was designed...
August 14, 2017: Biomacromolecules
https://www.readbyqxmd.com/read/28806273/the-changing-landscape-of-gene-editing-in-hematopoietic-stem-cells-a-step-towards-cas9-clinical-translation
#9
Daniel P Dever, Matthew H Porteus
PURPOSE OF REVIEW: Since the discovery two decades ago that programmable endonucleases can be engineered to modify human cells at single nucleotide resolution, the concept of genome editing was born. Now these technologies are being applied to therapeutically relevant cell types, including hematopoietic stem cells (HSC), which possess the power to repopulate an entire blood and immune system. The purpose of this review is to discuss the changing landscape of genome editing in hematopoietic stem cells (GE-HSC) from the discovery stage to the preclinical stage, with the imminent goal of clinical translation for the treatment of serious genetic diseases of the blood and immune system...
August 12, 2017: Current Opinion in Hematology
https://www.readbyqxmd.com/read/28805207/periodontal-diseases
#10
REVIEW
Denis F Kinane, Panagiota G Stathopoulou, Panos N Papapanou
Periodontal diseases comprise a wide range of inflammatory conditions that affect the supporting structures of the teeth (the gingiva, bone and periodontal ligament), which could lead to tooth loss and contribute to systemic inflammation. Chronic periodontitis predominantly affects adults, but aggressive periodontitis may occasionally occur in children. Periodontal disease initiation and propagation is through a dysbiosis of the commensal oral microbiota (dental plaque), which then interacts with the immune defences of the host, leading to inflammation and disease...
June 22, 2017: Nature Reviews. Disease Primers
https://www.readbyqxmd.com/read/28804866/virally-vectored-vaccine-delivery-medical-needs-mechanisms-advantages-and-challenges
#11
Daniel D Pinschewer
Vaccines represent one of the most successful chapters in the history of medicine. Over the past decades, the advent of recombinant cDNA technology has enabled the biomedical community to genetically engineer viruses for vaccine delivery purposes. As a starting point, this review evaluates the unmet medical needs, which drive scientists and industry to exploit such fundamentally new technology for human vaccination. The author discusses the molecular functioning, production and safety profile of replication-competent and -deficient viral vector systems, representing two fundamentally distinct classes of "genetic vaccines"...
August 14, 2017: Swiss Medical Weekly
https://www.readbyqxmd.com/read/28800157/generating-and-maintaining-transgenic-cryptosporidium-parvum-parasites
#12
Mattie C Pawlowic, Sumiti Vinayak, Adam Sateriale, Carrie F Brooks, Boris Striepen
The apicomplexan parasite Cryptosporidium is a leading cause of diarrheal disease and an important contributor to overall global child mortality. We currently lack effective treatment and immune prophylaxis. Recent advances now permit genetic modification of this important pathogen. We expect this to produce rapid advances in fundamental as well as translational research on cryptosporidiosis. Here we outline genetic engineering for Cryptosporidium in sufficient detail to establish transfection in any laboratory that requires access to this key technology...
August 11, 2017: Current Protocols in Microbiology
https://www.readbyqxmd.com/read/28799647/virulence-of-a-chimeric-recombinant-infectious-haematopoietic-necrosis-virus-expressing-the-spring-viraemia-of-carp-virus-glycoprotein-in-salmonid-and-cyprinid-fish
#13
E J Emmenegger, S Biacchesi, E Mérour, J A Glenn, A D Palmer, M Brémont, G Kurath
Infectious haematopoietic necrosis virus (IHNV) and spring viraemia of carp virus (SVCV) are both rhabdoviruses of fish, listed as notifiable disease agents by the World Organization for Animal Health. Recombinant rhabdoviruses with heterologous gene substitutions have been engineered to study genetic determinants and assess the potential of these recombinant viruses for vaccine development. A recombinant IHNV (rIHNV), containing the full-length genome of a European IHNV strain, was modified by deleting the glycoprotein (G) gene and replacing it with a European SVCV G-gene to make the rIHNV-Gsvcv...
August 11, 2017: Journal of Fish Diseases
https://www.readbyqxmd.com/read/28796529/designed-ankyrin-repeat-proteins-as-her2-targeting-domains-in-chimeric-antigen-receptor-engineered-t-cells
#14
Elizabeth Siegler, Si Li, Yu Jeong Kim, Pin Wang
Chimeric antigen receptor (CAR) engineering is a branch of cancer immunotherapy that equips immune cells to target tumor antigens expressed on the cell surface using antibody-derived single-chain variable fragments (scFvs). However, other antibody mimetics, such as designed ankyrin repeat proteins (DARPins), can also serve as antigen-binding domains in CARs. This study shows that CAR-engineered T (CAR-T) cells utilizing Her2-targeting DARPins G3 and 929 can target human epidermal growth factor receptor 2 (Her2)-overexpressing cancer cells as effectively as CAR-T cells with the scFv 4D5 in vitro, and G3 CAR-T cells can slow or eliminate tumor growth in vivo as effectively as 4D5 CAR-T cells...
June 22, 2017: Human Gene Therapy
https://www.readbyqxmd.com/read/28796297/transfer-of-tomato-immune-receptor-ve1-confers-ave1-dependent-verticillium-resistance-in-tobacco-and-cotton
#15
Yin Song, Linlin Liu, Yidong Wang, Dirk-Jan Valkenburg, Xianlong Zhang, Longfu Zhu, Bart P H J Thomma
Verticillium wilts caused by soil-borne fungal species of the Verticillium genus are economically important plant diseases that affect a wide range of host plants, and are notoriously difficult to combat. Perception of pathogen(-induced) ligands by plant immune receptors is a key component of plant innate immunity. In tomato, race-specific resistance to Verticillium wilt is governed by the cell surface-localized immune receptor Ve1 through recognition of the effector protein Ave1 that is secreted by race 1 strains of Verticillium spp...
August 10, 2017: Plant Biotechnology Journal
https://www.readbyqxmd.com/read/28795622/animal-models-for-periodontal-tissue-engineering-a-knowledge-generating-process
#16
Karim Mohamed Fawzy El-Sayed, Christof Doerfer
The human periodontium is a uniquely complex vital structure, supporting and anchoring the teeth in their alveolar sockets, playing thereby a decisive role in tooth homeostasis and function. Chronic periodontitis is a highly prevalent immune-inflammatory disease of the periodontium, affecting 15% of adult individuals and is characterized by progressive destruction of the periodontal tooth-investing tissues, culminating in their irreversible damage. Current periodontal evidence-based treatment strategies achieve periodontal healing via repair processes, mostly combating the inflammatory component of the disease, to halt or reduce prospective periodontal tissue loss...
August 10, 2017: Tissue Engineering. Part C, Methods
https://www.readbyqxmd.com/read/28794021/structure-based-design-of-hepatitis-c-virus-vaccines-that-elicit-neutralizing-antibody-responses-to-a-conserved-epitope
#17
Brian G Pierce, Elisabeth N Boucher, Kurt H Piepenbrink, Monir Ejemel, Chelsea A Rapp, William D Thomas, Eric J Sundberg, Zhiping Weng, Yang Wang
Despite recent advances in therapeutic options, hepatitis C virus (HCV) remains a severe global disease burden, and a vaccine can substantially reduce its incidence. Due to its extremely high sequence variability, HCV can readily escape the immune response, thus an effective vaccine must target conserved, functionally important epitopes. Using the structure of a broadly neutralizing antibody in complex with a conserved linear epitope from the HCV E2 envelope glycoprotein (residues 412-423; epitope I), we performed structure-based design of immunogens to induce antibody responses to this epitope...
August 9, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28793786/hemophilia-gene-therapy-ready-for-prime-time
#18
Thierry VandenDriessche, Marinee K L Chuah
Hemophilia A and B are congenital X-linked bleeding disorders caused by mutations in the genes encoding for the blood clotting factor VIII (FVIII) or factor IX (FIX), respectively. Since the beginning of gene therapy, hemophilia has been considered an attractive disease target that served as a trailblazer for the field at large. Different technologies have been explored to efficiently and safely deliver the therapeutic FVIII and FIX genes into the patients' cells. Currently, the most promising vectors for hemophilia gene therapy are adeno-associated viral vectors (AAV) and lentiviral vectors...
August 10, 2017: Human Gene Therapy
https://www.readbyqxmd.com/read/28793335/estimation-of-sickness-absenteeism-among-italian-healthcare-workers-during-seasonal-influenza-epidemics
#19
Maria Michela Gianino, Gianfranco Politano, Antonio Scarmozzino, Lorena Charrier, Marco Testa, Sebastian Giacomelli, Alfredo Benso, Carla Maria Zotti
OBJECTIVES: To analyze absenteeism among healthcare workers (HCWs) at a large Italian hospital and to estimate the increase in absenteeism that occurred during seasonal flu periods. DESIGN: Retrospective observational study. METHODS: The absenteeism data were divided into three "epidemic periods," starting at week 42 of one year and terminating at week 17 of the following year (2010-2011, 2011-2012, 2012-2013), and three "non-epidemic periods," defined as week 18 to week 41 and used as baseline data...
2017: PloS One
https://www.readbyqxmd.com/read/28782184/integrin-mediated-interactions-control-macrophage-polarization-in-3d-hydrogels
#20
Byung-Hyun Cha, Su Ryon Shin, Jeroen Leijten, Yi-Chen Li, Sonali Singh, Julie C Liu, Nasim Annabi, Reza Abdi, Mehmet R Dokmeci, Nihal Engin Vrana, Amir M Ghaemmaghami, Ali Khademhosseini
Adverse immune reactions prevent clinical translation of numerous implantable devices and materials. Although inflammation is an essential part of tissue regeneration, chronic inflammation ultimately leads to implant failure. In particular, macrophage polarity steers the microenvironment toward inflammation or wound healing via the induction of M1 and M2 macrophages, respectively. Here, this paper demonstrates that macrophage polarity within biomaterials can be controlled through integrin-mediated interactions between human monocytic THP-1 cells and collagen-derived matrix...
August 7, 2017: Advanced Healthcare Materials
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