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Antibody engineering

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https://www.readbyqxmd.com/read/29351125/central-inhibition-of-granulocyte-macrophage-colony-stimulating-factor-is-analgesic-in-experimental-neuropathic-pain
#1
Louise S C Nicol, Peter Thornton, Jon P Hatcher, Colin P Glover, Carl I Webster, Matthew Burrell, Kessia Hammett, Clare A Jones, Matthew A Sleeman, Andrew Billinton, Iain Chessell
With less than 50% of patients responding to the current standard of care and poor efficacy and selectivity of current treatments, neuropathic pain continues to be an area of considerable unmet medical need. Biological therapeutics such as monoclonal antibodies (mAbs) provide better intrinsic selectivity; however, delivery to the central nervous system (CNS) remains a challenge. Granulocyte-macrophage colony-stimulating factor (GM-CSF) is well described in inflammation-induced pain, and early-phase clinical trials evaluating its antagonism have exemplified its importance as a peripheral pain target...
January 16, 2018: Pain
https://www.readbyqxmd.com/read/29345977/targeted-and-nontargeted-%C3%AE-particle-therapies
#2
Michael R McDevitt, George Sgouros, Stavroula Sofou
α-Particle irradiation of cancerous tissue is increasingly recognized as a potent therapeutic option. We briefly review the physics, radiobiology, and dosimetry of α-particle emitters, as well as the distinguishing features that make them unique for radiopharmaceutical therapy. We also review the emerging clinical role of α-particle therapy in managing cancer and recent studies on in vitro and preclinical α-particle therapy delivered by antibodies, other small molecules, and nanometer-sized particles. In addition to their unique radiopharmaceutical characteristics, the increased availability and improved radiochemistry of α-particle radionuclides have contributed to the growing recent interest in α-particle radiotherapy...
January 18, 2018: Annual Review of Biomedical Engineering
https://www.readbyqxmd.com/read/29343613/restricted-hiv-1-env-glycan-engagement-by-lectin-reengineered-davei-protein-chimera-is-sufficient-for-lytic-inactivation-of-the-virus
#3
Bibek Parajuli, Kriti Acharya, Harry C Bach, Bijay Parajuli, Shiyu Zhang, Amos B Smith, Cameron F Abrams, Irwin Chaiken
We previously reported first generation recombinant DAVEI construct, a dual action virus entry inhibitor composed of cyanovirin-N (CVN) fused to a membrane proximal external region (MPER) or its derivative peptide Trp3. DAVEI exhibits potent and irreversible inactivation of HIV-1 viruses by dual engagement of gp120 and gp41. However, the promiscuity of CVN to associate with multiple glycosylation sites in gp120 and its multivalency limit current understanding of the molecular arrangement of the DAVEI molecules on trimeric spike...
January 17, 2018: Biochemical Journal
https://www.readbyqxmd.com/read/29341434/recombinant-collagen-scaffolds-as-substrates-for-human-neural-stem-progenitor-cells
#4
Richard A Que, Janahan Arulmoli, Nancy A Da Silva, Lisa A Flanagan, Szu-Wen Wang
Adhesion to the microenvironment profoundly affects stem cell functions, including proliferation and differentiation, and understanding the interaction of stem cells with the microenvironment is important for controlling their behavior. In this study, we investigated the effects of the integrin binding epitopes GFOGER and IKVAV (natively present in collagen I and laminin, respectively) on human neural stem/progenitor cells (hNSPCs). To test the specificity of these epitopes, GFOGER or IKVAV were placed within the context of recombinant triple-helical collagen III engineered to be devoid of native integrin binding sites...
January 17, 2018: Journal of Biomedical Materials Research. Part A
https://www.readbyqxmd.com/read/29339145/ocular-delivery-of-proteins-and-peptides-challenges-and-novel-formulation-approaches
#5
Abhirup Mandal, Dhananjay Pal, Vibhuti Agrahari, Hoang My Trinh, Mary Joseph, Ashim K Mitra
The impact of proteins and peptides on the treatment of various conditions including ocular diseases over the past few decades has been advanced by substantial breakthroughs in structural biochemistry, genetic engineering, formulation and delivery approaches. Formulation and delivery of proteins and peptides, such as monoclonal antibodies, aptamers, recombinant proteins and peptides to ocular tissues poses significant challenges owing to their large size, poor permeation and susceptibility to degradation. A wide range of advanced drug delivery systems including polymeric controlled release systems, cell-based delivery and nanowafers are being exploited to overcome the challenges of frequent administration to ocular tissues...
January 12, 2018: Advanced Drug Delivery Reviews
https://www.readbyqxmd.com/read/29337138/let-7-suppresses-b-cell-activation-through-restricting-the-availability-of-necessary-nutrients
#6
Shuai Jiang, Wei Yan, Shizhen Emily Wang, David Baltimore
The control of uptake and utilization of necessary extracellular nutrients-glucose and glutamine-is an important aspect of B cell activation. Let-7 is a family of microRNAs known to be involved in metabolic control. Here, we employed several engineered mouse models, including B cell-specific overexpression of Lin28a or the let-7a-1/let-7d/let-7f-1 cluster (let-7adf) and knockout of individual let-7 clusters to show that let-7adf specifically inhibits T cell-independent (TI) antigen-induced immunoglobulin (Ig)M antibody production...
January 10, 2018: Cell Metabolism
https://www.readbyqxmd.com/read/29335579/the-effects-of-antibody-engineering-ch-and-cl-in-trastuzumab-and-pertuzumab-recombinant-models-impact-on-antibody-production-and-antigen-binding
#7
Wai-Heng Lua, Wei-Li Ling, Joshua Yi Yeo, Jun-Jie Poh, David Philip Lane, Samuel Ken-En Gan
Current therapeutic antibodies such as Trastuzumab, are typically of the blood circulatory IgG1 class (Cκ/ CHγ1). Due to the binding to Her2 also present on normal cell surfaces, side effects such as cardiac failure can sometimes be associated with such targeted therapy. Using antibody isotype swapping, it may be possible to reduce systemic circulation through increased tissue localization, thereby minimising unwanted side effects. However, the effects of such modifications have yet to be fully characterized, particularly with regards to their biophysical properties in antigen binding...
January 15, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29333938/structure-based-engineering-to-restore-high-affinity-binding-of-an-isoform-selective-anti-tgf%C3%AE-1-antibody
#8
Dana M Lord, Julie J Bird, Denise M Honey, Annie Best, Anna Park, Ronnie R Wei, Huawei Qiu
Metelimumab (CAT192) is a human IgG4 monoclonal antibody developed as a TGFβ1-specific antagonist. It was tested in clinical trials for the treatment of scleroderma but later terminated due to lack of efficacy. Subsequent characterization of CAT192 indicated that its TGFβ1 binding affinity was reduced by ∼50-fold upon conversion from the parental single-chain variable fragment (scFv) to IgG4. We hypothesized this result was due to decreased conformational flexibility of the IgG that could be altered via engineering...
January 15, 2018: MAbs
https://www.readbyqxmd.com/read/29333729/immunoengineering-with-biomaterials-for-enhanced-cancer-immunotherapy
#9
REVIEW
Yu-Qing Xie, Lixia Wei, Li Tang
Cancer immunotherapy has recently shown dramatic clinical success inducing durable response in patients of a wide variety of malignancies. Further improvement of the clinical outcome with immune related cancer treatment requests more exquisite manipulation of a patient's immune system with increased immunity against diseases while mitigating the toxicities. To meet this challenge, biomaterials applied to immunoengineering are being developed to achieve tissue- and/or cell-specific immunomodulation and thus could potentially enhance both the efficacy and safety of current cancer immunotherapies...
January 14, 2018: Wiley Interdisciplinary Reviews. Nanomedicine and Nanobiotechnology
https://www.readbyqxmd.com/read/29329339/accessibility-and-contribution-to-glucan-masking-of-natural-and-genetically-tagged-versions-of-yeast-wall-protein-1-of-candida-albicans
#10
Bruce L Granger
Yeast wall protein 1 (Ywp1) is an abundant glycoprotein of the cell wall of the yeast form of Candida albicans, the most prevalent fungal pathogen of humans. Antibodies that bind to the polypeptide backbone of isolated Ywp1 show little binding to intact yeast cells, presumably because the Ywp1 epitopes are masked by the polysaccharides of the mannoproteins that form the outer layer of the cell wall. Rare cells do exhibit much greater anti-Ywp1 binding, however, and one of these was isolated and characterized...
2018: PloS One
https://www.readbyqxmd.com/read/29328884/evaluation-of-g2-citric-acid-based-dendrimer-as-an-adjuvant-in-veterinary-rabies-vaccine
#11
Vahid Asgary, Alireza Shoari, Majid Afshar Moayad, Mehdi Shafiee Ardestani, Razieh Bigdeli, Leila Ghazizadeh, Mohammad Sadeq Khosravy, Erfan Panahnejad, Alireza Janani, Rouzbeh Bashar, Maliheh Abedi, Reza Ahangari Cohan
For induction of an appropriate immune response, especially in the case of an inactivated vaccine, the use of an adjuvant is crucial. In this study, adjuvanticity effect of G2 dendrimer in veterinary rabies vaccine has been investigated. A nonlinear globular G2 dendrimer comprising citric acid and polyethylene glycol 600 (PEG-600) was synthesized and the toxicity was studied in vitro on the J774A.1 cell line. The adjuvanticity effect of the dendrimer was then investigated on rabies virus in NMRI mice as a model...
January 2018: Viral Immunology
https://www.readbyqxmd.com/read/29328338/binding-affinity-prediction-of-nanobody-protein-complexes-by-scoring-of-molecular-dynamics-trajectories
#12
Miguel A Soler, Sara Fortuna, Ario de Marco, Alessandro Laio
Nanobodies offer a viable alternative to antibodies for engineering high affinity binders. Their small size has an additional advantage: it allows exploiting computational protocols for optimizing their biophysical features, such as the binding affinity. The efficient prediction of this quantity is still considered a daunting task especially for modelled complexes. We show how molecular dynamics can successfully assist in the binding affinity prediction of modelled nanobody-protein complexes. The approximate initial configurations obtained by in silico design must undergo large rearrangements before achieving a stable conformation, in which the binding affinity can be meaningfully estimated...
January 12, 2018: Physical Chemistry Chemical Physics: PCCP
https://www.readbyqxmd.com/read/29327758/a-computational-analysis-of-pro-angiogenic-therapies-for-peripheral-artery-disease
#13
Lindsay E Clegg, Feilim Mac Gabhann
Inducing therapeutic angiogenesis to effectively form hierarchical, non-leaky networks of perfused vessels in tissue engineering applications and ischemic disease remains an unmet challenge, despite extensive research and multiple clinical trials. Here, we use a previously-developed, multi-scale, computational systems pharmacology model of human peripheral artery disease to screen a diverse array of promising pro-angiogenic strategies, including gene therapy, biomaterials, and antibodies. Our previously-validated model explicitly accounts for VEGF immobilization, Neuropilin-1 binding, and weak activation of VEGF receptor 2 (VEGFR2) by the "VEGFxxxb" isoforms...
January 12, 2018: Integrative Biology: Quantitative Biosciences From Nano to Macro
https://www.readbyqxmd.com/read/29326157/targeting-b-cells-and-plasma-cells-in-glomerular-diseases-translational-perspectives
#14
Eva Schrezenmeier, David Jayne, Thomas Dörner
The unique contributions of memory B cells and plasma cells in kidney diseases remain unclear. In this review, we evaluate the clinical experience with treatments directed at B cells, such as rituximab, and at plasma cells, such as proteasome inhibition, to shed light on the role of these two B lineage compartments in glomerular diseases. Specifically, analysis of these targeted interventions in diseases such as ANCA-associated vasculitis, SLE, and antibody-mediated transplant rejection permits insight into the pathogenetic effect of these cells...
January 11, 2018: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/29325564/engineered-recombinant-protein-products-of-the-avian-paramyxovirus-type-1-nucleocapsid-and-phosphoprotein-genes-for-serological-diagnosis
#15
Na Zhao, Christian Grund, Martin Beer, Timm C Harder
BACKGROUND: Virulent Newcastle disease virus (NDV, avian Avulavirus-1, APMV-1) induces a highly contagious and lethal systemic disease in gallinaceous poultry. APMV-1 antibody detection is used for surveillance and to control vaccination, but is hampered by cross-reactivity to other subtypes of avian Avulaviruses. Data are lacking concerning the applicability of NDV V proteins as differential diagnostic marker to distinguish vaccinated from virus-infected birds (DIVA strategy). METHODS: Full length and C-terminally truncated nucleocapsid (NP) protein, and the unique C-terminal regions of the phospho- (P) and V proteins of the NDV LaSota strain were bacterially expressed as fusion proteins with the multimerization domain of the human C4 binding protein, and used as diagnostic antigens in indirect ELISA...
January 11, 2018: Virology Journal
https://www.readbyqxmd.com/read/29324849/the-b-cell-death-function-of-obinutuzumab-hdel-produced-in-plant-nicotiana-benthamiana-l-is-equivalent-to-obinutuzumab-produced-in-cho-cells
#16
Jin Won Lee, Woon Heo, Jinu Lee, Narae Jin, Sei Mee Yoon, Ki Youl Park, Eun Yu Kim, Woo Taek Kim, Joo Young Kim
Plants have attracted attention as bio-drug production platforms because of their economical and safety benefits. The preliminary efficacy of ZMapp, a cocktail of antibodies produced in N. benthamiana (Nicotiana benthamiana L.), suggested plants may serve as a platform for antibody production. However, because the amino acid sequences of the Fab fragment are diverse and differences in post-transcriptional processes between animals and plants remain to be elucidated, it is necessary to confirm functional equivalence of plant-produced antibodies to the original antibody...
2018: PloS One
https://www.readbyqxmd.com/read/29321208/engineered-synthetic-antibodies-as-probes-to-quantify-the-energetic-contributions-of-ligand-binding-to%C3%A2-conformational-changes-in-proteins
#17
Somnath Mukherjee, Dionne H Griffin, James R Horn, Shahir S Rizk, Malgorzata Nocula-Lugowska, Magnus Malmqvist, Sangwoo S Kim, Anthony A Kossiakoff
Conformational changes in proteins due to ligand binding are ubiquitous in biological systems and are integral to many biological systems. However, it is often challenging to link ligand-induced conformational changes to a resulting biological function because it is difficult to distinguish between the energetic components associated with ligand-binding and those due to structural rearrangements. Here, we used a  unique approach exploiting conformation-specific and regio-specific synthetic antibodies (sABs) to probe the energetic contributions of ligand-binding to conformation changes...
January 10, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29318789/methods-and-advances-on-antibodies-metabolic-engineering-3d-models-diagnostics-imaging-and-more
#18
EDITORIAL
Uta Göbel, Jing Zhu
No abstract text is available yet for this article.
January 2018: Biotechnology Journal
https://www.readbyqxmd.com/read/29317736/development-and-characterization-of-a-novel-luciferase-based-cytotoxicity-assay
#19
Hittu Matta, Ramakrishnan Gopalakrishnan, Sunju Choi, Rekha Prakash, Venkatesh Natarajan, Ruben Prins, Songjie Gong, Saurabh D Chitnis, Michael Kahn, Xu Han, Vishan Chaudhary, Adam Soni, Jennifer Sernas, Prottasha Khan, Dan Wang, Preet M Chaudhary
A simple, accurate, sensitive and robust assay that can rapidly and specifically measure the death of target cells would have applications in many areas of biomedicine and particularly for the development of novel cellular- and immune-therapeutics. In this study, we describe a novel cytotoxicity assay, termed the Matador assay, which takes advantage of the extreme brightness, stability and glow-like characteristics of recently discovered novel marine luciferases and their engineered derivatives. The assay involves expression of a luciferase of interest in target cells in a manner so that it is preferentially retained within the healthy cells but is either released from dead and dying cells or whose activity can be preferentially measured in dead and dying cells...
January 9, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29316610/development-of-a-deimmunized-bispecific-immunotoxin-ddt2219-against-b-cell-malignancies
#20
Joerg U Schmohl, Deborah Todhunter, Elizabeth Taras, Veronika Bachanova, Daniel A Vallera
Diphtheria toxin (DT) related targeted toxins are effective in cancer treatment, but efficacy diminishes in time because of their immunogenic potential and/or former vaccinations. In order to overcome this limitation for DT2219, a promising bispecific targeted toxin which targets CD19 and CD22, we deimmunized the DT moiety, and thereby developed an exciting improved drug (dDT2219) which still has the potential to sufficiently target B-cell malignancies but also limits clearance because of its reduced immunogenicity...
January 6, 2018: Toxins
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