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Engineered immune cells

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https://www.readbyqxmd.com/read/29333729/immunoengineering-with-biomaterials-for-enhanced-cancer-immunotherapy
#1
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
#2
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
#3
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/29326244/gene-therapy-comes-of-age
#4
REVIEW
Cynthia E Dunbar, Katherine A High, J Keith Joung, Donald B Kohn, Keiya Ozawa, Michel Sadelain
After almost 30 years of promise tempered by setbacks, gene therapies are rapidly becoming a critical component of the therapeutic armamentarium for a variety of inherited and acquired human diseases. Gene therapies for inherited immune disorders, hemophilia, eye and neurodegenerative disorders, and lymphoid cancers recently progressed to approved drug status in the United States and Europe, or are anticipated to receive approval in the near future. In this Review, we discuss milestones in the development of gene therapies, focusing on direct in vivo administration of viral vectors and adoptive transfer of genetically engineered T cells or hematopoietic stem cells...
January 12, 2018: Science
https://www.readbyqxmd.com/read/29326157/targeting-b-cells-and-plasma-cells-in-glomerular-diseases-translational-perspectives
#5
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/29323870/cell-membrane-bioconjugation-and-membrane-derived-nanomaterials-for-immunotherapy
#6
Peter Y Li, Zhiyuan Fan, Hao Cheng
Cell membrane engineering, including live cell membrane bioconjugation and cell membrane-derived nanomaterials is a highly promising strategy to modulate immune responses for treating diseases. Many cell membrane engineering methods have potential for translation for human clinical use in the near future. In this Topical Review, we summarize the cell membrane conjugation strategies that have been investigated for cancer immunotherapy, the prevention of immune rejection to donor cells and tissues, and the induction of antigen-specific tolerance in autoimmune diseases...
January 11, 2018: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/29323144/defining-tissue-proteomes-by-systematic-literature-review
#7
Sarah A Hibbert, Matiss Ozols, Christopher E M Griffiths, Rachel E B Watson, Mike Bell, Michael J Sherratt
Defining protein composition is a key step in understanding the function of both healthy and diseased biological systems. There is currently little consensus between existing published proteomes in tissues such as the aorta, cartilage and organs such as skin. Lack of agreement as to both the number and identity of proteins may be due to issues in protein extraction, sensitivity/specificity of detection and the use of disparate tissue/cell sources. Here, we developed a method combining bioinformatics and systematic review to screen >32M articles from the Web of Science for evidence of proteins in healthy human skin...
January 11, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29322086/engineered-livers-for-infectious-diseases
#8
REVIEW
Nil Gural, Liliana Mancio-Silva, Jiang He, Sangeeta N Bhatia
Engineered liver systems come in a variety of platform models, from 2-dimensional cocultures of primary human hepatocytes and stem cell-derived progeny, to 3-dimensional organoids and humanized mice. Because of the species-specificity of many human hepatropic pathogens, these engineered systems have been essential tools for biologic discovery and therapeutic agent development in the context of liver-dependent infectious diseases. Although improvement of existing models is always beneficial, and the addition of a robust immune component is a particular need, at present, considerable progress has been made using this combination of research platforms...
2018: Cellular and Molecular Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/29321630/engineered-mesenchymal-stem-cell-sheets-patches-prevents-postoperative-pancreatic-leakage-in-a-rat-model
#9
Seong-Ryong Kim, Hye-Jin Yi, Yu Na Lee, Ji Yoon Park, Robert M Hoffman, Teruo Okano, In Kyong Shim, Song Cheol Kim
Post-operative pancreatic fistula (POPF) following pancreatic resection is a life-threatening surgical complication. Cell sheets were prepared and harvested using temperature-responsive culture dishes and transplanted as patches to seal POPF. Two different mesenchymal stem cell (MSC) sheets were compared in terms of the preventative ability for pancreatic leakage in a rat model. Both rat adipose-derived stem cell (rADSC) and bone marrow-derived stem cell (rBMSC) sheets were transplanted. Those rADSC and rBMSC sheets are created without enzymes and thus maintained their cell-cell junctions and adhesion proteins with intact fibronectin on the basal side, as well as characteristics of MSCs...
January 10, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29317736/development-and-characterization-of-a-novel-luciferase-based-cytotoxicity-assay
#10
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
#11
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
https://www.readbyqxmd.com/read/29315824/cytokine-secreting-microparticles-engineer-the-fate-and-the-effector-functions-of-t-cells
#12
Fatemeh S Majedi, Mohammad Mahdi Hasani-Sadrabadi, Yoko Kidani, Timothy J Thauland, Alireza Moshaverinia, Manish J Butte, Steven J Bensinger, Louis-S Bouchard
T-cell immunotherapy is a promising approach for cancer, infection, and autoimmune diseases. However, significant challenges hamper its therapeutic potential, including insufficient activation, delivery, and clonal expansion of T-cells into the tumor environment. To facilitate T-cell activation and differentiation in vitro, core-shell microparticles are developed for sustained delivery of cytokines. These particles are enriched by heparin to enable a steady release of interleukin-2 (IL-2), the major T-cell growth factor, over 10+ d...
January 8, 2018: Advanced Materials
https://www.readbyqxmd.com/read/29315532/treatment-of-mcpt8dtr-mice-with-high-or-low-dose-diphtheria-toxin-leads-to-differential-depletion-of-basophils-and-granulocyte-macrophage-progenitors
#13
Carole El Hachem, Pierre Hener, Peggy Kirstetter, Jiagui Li, Susan Chan, Mei Li
Basophils have been recently recognized to play important roles in type 2 immune responses during allergies and parasitic infection, largely due to the development of novel tools for the in vivo study of these cells. As such, the genetically-engineered MCPT8DTR mouse line has been used to specifically deplete basophils following treatment with diphtheria toxin (DT). In this study, we showed that DT-injected MCPT8DTR mice exhibited a striking decrease of eosinophils and neutrophils in skin when subjected to a hapten fluorescein isothiocyanate (FITC)-induced allergic contact dermatitis (ACD) experimental protocol...
January 8, 2018: European Journal of Immunology
https://www.readbyqxmd.com/read/29315015/tumor-specific-t-cells-engineered-to-overcome-tumor-immune-evasion-induce-clinical-responses-in-patients-with-relapsed-hodgkin-lymphoma
#14
Catherine M Bollard, Tamara Tripic, Conrad Russell Cruz, Gianpietro Dotti, Stephen Gottschalk, Vicky Torrano, Olga Dakhova, George Carrum, Carlos A Ramos, Hao Liu, Meng-Fen Wu, Andrea N Marcogliese, Cecilia Barese, Youli Zu, Daniel Y Lee, Owen O'Connor, Adrian P Gee, Malcolm K Brenner, Helen E Heslop, Cliona M Rooney
Purpose Transforming growth factor-β (TGF-β) production in the tumor microenvironment is a potent and ubiquitous tumor immune evasion mechanism that inhibits the expansion and function of tumor-directed responses; therefore, we conducted a clinical study to discover the effects of the forced expression of a dominant-negative TGF-β receptor type 2 (DNRII) on the safety, survival, and activity of infused tumor-directed T cells. Materials and Methods In a dose escalation study, eight patients with Epstein Barr virus-positive Hodgkin lymphoma received two to 12 doses of between 2 × 107 and 1...
January 9, 2018: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/29313037/soluble-collagen-vi-treatment-enhances-mesenchymal-stem-cells-expansion-for-engineering-cartilage
#15
Piera Smeriglio, Jieun Lee, Nidhi Bhutani
Bone Marrow-derived mesenchymal stem cells (BM-MSC) are an attractive source for cell-based therapies in cartilage injury owing to their efficient differentiation into chondrocytes and their immune-suppressive abilities. However, their clinical use is hampered by a scarcity of cells leading to compromised efficacy. While expansion of human MSC ex vivo can potentially overcome the scarcity of cells, current methods lead to a rapid loss of the stem cell properties. In this study, we report soluble Collagen VI (cartilage pericellular matrix component) as a potential biologic that can expand the MSC population while maintaining the stem cell phenotype as confirmed by expression of the stem cell markers CD105 and CD90...
September 2017: Bioengineering & Translational Medicine
https://www.readbyqxmd.com/read/29311474/enantioselective-monoclonal-antibodies-for-detecting-ketamine-to-crack-down-on-illicit-use
#16
Izumi Morita, Hiroyuki Oyama, Yui Kanda, Mayumi Yasuo, Aya Ito, Masahiro Toyota, Yoshinori Hayashi, Takeshi Yokoyama, Norihiro Kobayashi
Ketamine (KT) is a chiral anesthetic agent, (R)- and (S)-enantiomers of which differ in their pharmacological properties. KT has become one of the most commonly used illicit drugs in the world, thus, rapid and feasible on-site testing is required to crack down on the illicit use. Although immunochemical approach with specific antibodies is promising for this purpose, in practice anti-KT antibodies are difficult to obtain. We here disclose generation of monoclonal antibodies against KT. Mice were immunized with either (a) commercially-available or (b) in-house-prepared KT-albumin conjugates...
2018: Biological & Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/29311380/hitting-the-target-how-t-cells-detect-and-eliminate-tumors
#17
REVIEW
Anthony E Zamora, Jeremy Chase Crawford, Paul G Thomas
The successes of antitumor immuno-based therapies and the application of next-generation sequencing to mutation profiling have produced insights into the specific targets of antitumor T cells. Mutated proteins have tremendous potential as targets for interventions using autologous T cells or engineered cell therapies and may serve as important correlates of efficacy for immunoregulatory interventions including immune checkpoint blockade. As mutated self, tumors present an exceptional case for host immunity, which has primarily evolved in response to foreign pathogens...
January 15, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29310916/chimeric-antigen-receptor-engineered-human-gamma-delta-t-cells-enhanced-cytotoxicity-with-retention-of-cross-presentation
#18
Anna Capsomidis, Gabriel Benthall, Heleen H Van Acker, Jonathan Fisher, Anne M Kramer, Zarah Abeln, Yvonne Majani, Talia Gileadi, Rebecca Wallace, Kenth Gustafsson, Barry Flutter, John Anderson
Gamma delta T (γδT) lymphocytes are primed for rapid function, including cytotoxicity toward cancer cells, and are a component of the immediate stress response. Following activation, they can function as professional antigen-presenting cells. Chimeric antigen receptors (CARs) work by focusing T cell function on defined cell surface tumor antigens and provide essential costimulation for robust activation. Given the natural tropism of γδT cells for the tumor microenvironment, we hypothesized that their transduction with CARs might enhance cytotoxicity while retaining their ability to migrate to tumor and act as antigen-presenting cells to prolong the intratumoral immune response...
December 8, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/29305506/contribution-of-ytha-a-pspc-family-transcriptional-regulator-to-lactococcus-lactis-f44-acid-tolerance-and-nisin-yield-a-transcriptomic-approach
#19
Hao Wu, Jingui Liu, Sen Miao, Yue Zhao, Hongji Zhu, Mingqiang Qiao, Per Erik Joakim Saris, Jianjun Qiao
To overcome the adverse impacts of environmental stresses during growth, different adaptive regulation mechanisms can be activated in Lactococcus lactis In this study, the transcription levels of eight transcriptional regulators of L. lactis subsp. lactis F44 under acid stress was analyzed using qRT-PCR. Eight overexpressed strains were then constructed to examine their influences on acid resistant capability. Overexpressing ythA, a PspC family transcriptional regulator, increased the survival rate by 3.2-fold compared with the control at the lethal pH 3...
January 5, 2018: Applied and Environmental Microbiology
https://www.readbyqxmd.com/read/29305085/engineering-the-delivery-system-for-crispr-based-genome-editing
#20
REVIEW
Zachary Glass, Matthew Lee, Yamin Li, Qiaobing Xu
Clustered regularly interspaced short palindromic repeat-CRISPR-associated protein (CRISPR-Cas) systems, found in nature as microbial adaptive immune systems, have been repurposed into an important tool in biological engineering and genome editing, providing a programmable platform for precision gene targeting. These tools have immense promise as therapeutics that could potentially correct disease-causing mutations. However, CRISPR-Cas gene editing components must be transported directly to the nucleus of targeted cells to exert a therapeutic effect...
January 2, 2018: Trends in Biotechnology
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