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Engineered immune cells

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https://www.readbyqxmd.com/read/29150767/cell-migration-in-1d-and-2d-nanofiber-microenvironments
#1
Horacio M Estabridis, Aniket Jana, Amrinder Nain, David J Odde
Understanding how cells migrate in fibrous environments is important in wound healing, immune function, and cancer progression. A key question is how fiber orientation and network geometry influence cell movement. Here we describe a quantitative, modeling-based approach toward identifying the mechanisms by which cells migrate in fibrous geometries having well controlled orientation. Specifically, U251 glioblastoma cells were seeded onto non-electrospinning Spinneret based tunable engineering parameters fiber substrates that consist of networks of suspended 400 nm diameter nanofibers...
November 17, 2017: Annals of Biomedical Engineering
https://www.readbyqxmd.com/read/29150718/re-educating-immunity-in-respiratory-allergies-the-potential-for-hematopoietic-stem-cell-mediated-gene-therapy
#2
REVIEW
Jeremy F Brooks, Janet M Davies, James W Wells, Raymond J Steptoe
Respiratory allergies represent a significant disease burden worldwide affecting up to 300 million people globally. Medication and avoidance of known triggers do not address the underlying pathology. Traditional immunotherapies for allergy aim to reinstate immune homeostasis but require years of treatment and have poor long-term efficacy. Novel approaches, such as gene-engineered hematopoietic stem cell transplantation, induce profound antigen-specific tolerance in autoimmunity. Recent evidence shows this approach may also have therapeutic utility for allergy...
November 17, 2017: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
https://www.readbyqxmd.com/read/29150002/gene-editing-and-crispr-therapeutics-strategies-taught-by-cell-and-gene-therapy
#3
Juan C Ramirez
A few years ago, we assisted in the demonstration for the first time of the revolutionary idea of a type of adaptive-immune system in the bacteria kingdom. This system, named CRISPR, and variants engineered in the lab, have been demonstrated as functional with extremely high frequency and fidelity in almost all eukaryotic cells studied to date. The capabilities of this RNA-guided nuclease have added to the interest that was announced with the advent of previous technologies for genome editing tools, such as ZFN and TALEN...
2017: Progress in Molecular Biology and Translational Science
https://www.readbyqxmd.com/read/29147628/trial-watch-adoptively-transferred-cells-for-anticancer-immunotherapy
#4
REVIEW
Carole Fournier, François Martin, Laurence Zitvogel, Guido Kroemer, Lorenzo Galluzzi, Lionel Apetoh
Immunotherapies aimed at strengthening immune effector responses against malignant cells are growing at exponential rates. Alongside, the impressive benefits obtained by patients with advanced melanoma who received adoptively transferred tumor-infiltrating lymphocytes (TILs) have encouraged the scientific community to pursue adoptive cell transfer (ACT)-based immunotherapy. ACT involves autologous or allogenic effector lymphocytes that are generally obtained from the peripheral blood or resected tumors, expanded and activated ex vivo, and administered to lymphodepleted patients...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/29147558/discovery-and-design-of-self-assembling-peptides
#5
REVIEW
Shuguang Zhang
Peptides are ubiquitous in nature and useful in many fields, from agriculture as pesticides, in medicine as antibacterial and antifungal drugs founded in the innate immune systems, to medicinal chemistry as hormones. However, the concept of peptides as materials was not recognized until 1990 when a self-assembling peptide as a repeating segment in a yeast protein was serendipitously discovered. Peptide materials are so called because they have bona fide materials property and are made from simple amino acids with well-ordered nanostructures under physiological conditions...
December 6, 2017: Interface Focus
https://www.readbyqxmd.com/read/29146244/extending-antigen-release-from-particulate-vaccines-results-in-enhanced-antitumor-immune-response
#6
Chintan H Kapadia, Shaomin Tian, Jillian L Perry, David Sailer, J Christopher Luft, Joseph M DeSimone
Tumor-specific CD8(+) cytotoxic T lymphocytes (CTLs) play a critical role in an anti-tumor immune response. However, vaccination intended to elicit a potent CD8(+) T cell responses employing tumor-associated peptide antigens, are typically ineffective due to poor immunogenicity. Previously, we engineered a polyethylene glycol (PEG) hydrogel-based subunit vaccine for the delivery of an antigenic peptide and CpG (adjuvant) to elicit potent CTLs. In this study, we further examined the effect of antigen release kinetics on their induced immune responses...
November 13, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/29145997/correlation-of-graft-immune-composition-with-outcomes-after-allogeneic-stem-cell-transplantation-moving-towards-a-perfect-transplant
#7
REVIEW
Guang Gu, Jian-Zhu Yang, Li-Xia Sun
Allogeneic stem cell transplantation (allo-SCT) offers an important curative therapy for hematological malignancies and other diseases. A number of studies have demonstrated the association of immune compositions in allografts with outcomes after allo-SCT, which promote graft engineering to improve transplant prognosis. This review summarizes the advances in investigating the correlation of the graft immune compositions with transplant outcomes in different transplant modalities, focusing on the immune subsets likely to have the greatest impact on clinical outcomes...
November 7, 2017: Cellular Immunology
https://www.readbyqxmd.com/read/29143002/nanotopography-based-strategy-for-the-precise-manipulation-of-osteoimmunomodulation-in-bone-regeneration
#8
REVIEW
Zetao Chen, Akash Bachhuka, Fei Wei, Xiaoshuang Wang, Guanqi Liu, Krasimir Vasilev, Yin Xiao
Immune cells play vital roles in regulating bone dynamics. Successful bone regeneration requires a favourable osteo-immune environment. The high plasticity and diversity of immune cells make it possible to manipulate the osteo-immune response of immune cells, thus modulating the osteoimmune environment and regulating bone regeneration. With the advancement in nanotechnology, nanotopographies with different controlled surface properties can be fabricated. On tuning the surface properties, the osteo-immune response can be precisely modulated...
November 16, 2017: Nanoscale
https://www.readbyqxmd.com/read/29142300/structure-and-immunogenicity-of-pre-fusion-stabilized-human-metapneumovirus-f-glycoprotein
#9
Michael B Battles, Vicente Más, Eduardo Olmedillas, Olga Cano, Mónica Vázquez, Laura Rodríguez, José A Melero, Jason S McLellan
Human metapneumovirus (hMPV) is a frequent cause of bronchiolitis in young children. Its F glycoprotein mediates virus-cell membrane fusion and is the primary target of neutralizing antibodies. The inability to produce recombinant hMPV F glycoprotein in the metastable pre-fusion conformation has hindered structural and immunological studies. Here, we engineer a pre-fusion-stabilized hMPV F ectodomain and determine its crystal structure to 2.6 Å resolution. This structure reveals molecular determinants of strain-dependent acid-induced fusion, as well as insights into refolding from pre- to post-fusion conformations...
November 16, 2017: Nature Communications
https://www.readbyqxmd.com/read/29141886/pd-l1-genetic-overexpression-or-pharmacological-restoration-in-hematopoietic-stem-and-progenitor-cells-reverses-autoimmune-diabetes
#10
Moufida Ben Nasr, Sara Tezza, Francesca D'Addio, Chiara Mameli, Vera Usuelli, Anna Maestroni, Domenico Corradi, Silvana Belletti, Luca Albarello, Gabriella Becchi, Gian Paolo Fadini, Christian Schuetz, James Markmann, Clive Wasserfall, Leonard Zon, Gian Vincenzo Zuccotti, Paolo Fiorina
Immunologically based clinical trials performed thus far have failed to cure type 1 diabetes (T1D), in part because these approaches were nonspecific. Because the disease is driven by autoreactive CD4 T cells, which destroy β cells, transplantation of hematopoietic stem and progenitor cells (HSPCs) has been recently offered as a therapy for T1D. Our transcriptomic profiling of HSPCs revealed that these cells are deficient in programmed death ligand 1 (PD-L1), an important immune checkpoint, in the T1D nonobese diabetic (NOD) mouse model...
November 15, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/29139088/contrasting-views-on-the-role-of-mesenchymal-stromal-stem-cells-in-tumour-growth-a-systematic-review-of-experimental-design
#11
Ahmed Kolade Oloyo, Melvin Anyasi Ambele, Michael Sean Pepper
The effect of mesenchymal stromal/stem cells (MSCs) on tumour growth remains controversial. Experimental evidence supports both an inhibitory and a stimulatory effect. We have assessed factors responsible for the contrasting effects of MSCs on tumour growth by doing a meta-analysis of existing literature between 2000 and May 2017. We assessed 183 original research articles comprising 338 experiments. We considered (a) in vivo and in vitro experiments, (b) whether in vivo studies were syngeneic or xenogeneic, and (c) if animals were immune competent or deficient...
November 15, 2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/29133624/histopathological-histomorphometrical-and-radiological-evaluations-of-hydroxyapatite-bioactive-glass-and-fluorapatite-bioactive-glass-nanocomposite-foams-as-cell-scaffolds-in-rat-tibia-an-in-vivo-study
#12
Maryam Seyedmajidi, Sina Haghanifar, Karimollah Hajian-Tilaki, Seyedali Seyedmajidi
Bone defects are common and persistent problems in clinical orthopedics and dentistry. The development of synthetic reconstruction materials is essential owing to the restricted access to natural bone grafts, disease transmission risks, surgical costs, donor-site morbidity, infections, and immune response-related complications. Accordingly, the aim of the present study was to evaluate the histopathological, histomorphometrical, and radiological characteristics of composite foams containing hydroxyapatite/bioactive glass (HA/BG) and fluorapatite/bioactive glass (FA/BG) as cell scaffolds in rat tibia reconstruction...
November 14, 2017: Biomedical Materials
https://www.readbyqxmd.com/read/29131519/displaying-tetra-membrane-spanning-claudins-on-enveloped-virus-like-particles-for-cancer-immunotherapy
#13
Irene C Schneider, Jessica Hartmann, Gundula Braun, Jörn Stitz, Thorsten Klamp, Mahjoub Bihi, Ugur Sahin, Christian J Buchholz
Virus-like particles (VLPs) displaying foreign antigens have become an important tool in vaccination including the induction of immune responses against self-antigens. Claudin 6 (CLDN6) has been identified as tumor-associated antigen and is therefore a potential target for tumor vaccination strategies. However, as tetra-membrane spanning protein its incorporation into VLPs while preserving a native fold is challenging. Here, we attempted the incorporation of a panel of engineered CLDN6 variants into the membrane of retrovirus-derived VLPs...
November 13, 2017: Biotechnology Journal
https://www.readbyqxmd.com/read/29131143/nonimmune-cells-equipped-with-t-cell-receptor-like-signaling-for-cancer-cell-ablation
#14
Ryosuke Kojima, Leo Scheller, Martin Fussenegger
The ability to engineer custom cell-contact-sensing output devices into human nonimmune cells would be useful for extending the applicability of cell-based cancer therapies and for avoiding risks associated with engineered immune cells. Here we have developed a new class of synthetic T-cell receptor-like signal-transduction device that functions efficiently in human nonimmune cells and triggers release of output molecules specifically upon sensing contact with a target cell. This device employs an interleukin signaling cascade, whose OFF/ON switching is controlled by biophysical segregation of a transmembrane signal-inhibitory protein from the sensor cell-target cell interface...
November 13, 2017: Nature Chemical Biology
https://www.readbyqxmd.com/read/29130151/viral-vectors-engineered-cells-and-the-crispr-revolution
#15
James E DiCarlo, Anurag Deeconda, Stephen H Tsang
Over the past few decades the ability to edit human cells has revolutionized modern biology and medicine. With advances in genome editing methodologies, gene delivery and cell-based therapeutics targeted at treatment of genetic disease have become a reality that will become more and more essential in clinical practice. Modifying specific mutations in eukaryotic cells using CRISPR-Cas systems derived from prokaryotic immune systems has allowed for precision in correcting various disease mutations. Furthermore, delivery of genetic payloads by employing viral tropism has become a crucial and effective mechanism for delivering genes and gene editing systems into cells...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/29128214/application-of-whey-protein-isolate-in-bone-regeneration-effects-on-growth-and-osteogenic-differentiation-of-bone-forming-cells
#16
Timothy E L Douglas, Marta Vandrovcová, Nikola Kročilová, Julia K Keppler, Jana Zárubová, Andre G Skirtach, Lucie Bačáková
Recently, milk-derived proteins have attracted attention for applications in the biomedical field such as tissue regeneration. Whey protein isolate (WPI), especially its main component β-lactoglobulin, can modulate immunity and acts as an antioxidant, antitumor, antiviral, and antibacterial agent. There are very few reports of the application of WPI in tissue engineering, especially in bone tissue engineering. In this study, we tested the influence of different concentrations of WPI on behavior of human osteoblast-like Saos-2 cells, human adipose tissue-derived stem cells (ASC), and human neonatal dermal fibroblasts (FIB)...
November 8, 2017: Journal of Dairy Science
https://www.readbyqxmd.com/read/29127433/targeting-and-suppression-of-her3-positive-breast-cancer-by-t-lymphocytes-expressing-a-heregulin-chimeric-antigen-receptor
#17
Bai-Le Zuo, Bo Yan, Guo-Xu Zheng, Wen-Jin Xi, Xiao Zhang, An-Gang Yang, Lin-Tao Jia
Chimeric antigen receptor-modulated T lymphocytes (CAR-T) have emerged as a powerful tool for arousing anticancer immunity. Endogenous ligands for tumor antigen may outperform single-chain variable fragments to serve as a component of CARs with high cancer recognition efficacy and minimized immunogenicity. As heterodimerization and signaling partners for human epidermal growth factor receptor 2 (HER2), HER3/HER4 has been implicated in tumorigenic signaling and therapeutic resistance of breast cancer. In this study, we engineered T cells with a CAR consisting of the extracellular domain of heregulin-1β (HRG1β) that is a natural ligand for HER3/HER4, and evaluated the specific cytotoxicity of these CAR-T cells in cultured HER3 positive breast cancer cells and xenograft tumors...
November 10, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/29124929/injectable-polymeric-cytokine-binding-nanowires-are-effective-tissue-specific-immunomodulators
#18
Colin R Zamecnik, Margaret M Lowe, David M Patterson, Michael D Rosenblum, Tejal A Desai
Injectable nanomaterials that interact with the host immune system without surgical intervention present spatially anchored complements to cell transplantation and could offer improved pharmacokinetics compared to systemic cytokine therapy. Here we demonstrate fabrication of high aspect ratio polycaprolactone nanowires coupled with cytokine-binding antibodies that assemble into porous matrices when injected into the subcutaneous space. These structures are fabricated using a nanotemplating technique that allows for tunability of particle dimensions and utilize a straightforward maleimide conjugation chemistry to allow site-specific coupling to proteins...
November 15, 2017: ACS Nano
https://www.readbyqxmd.com/read/29123959/immunological-efficacy-of-glypican-3-peptide-vaccine-in-patients-with-advanced-hepatocellular-carcinoma
#19
Nobuhiro Tsuchiya, Toshiaki Yoshikawa, Norihiro Fujinami, Keigo Saito, Shoichi Mizuno, Yu Sawada, Itaru Endo, Tetsuya Nakatsura
We have previously conducted a phase I trial to test the efficacy of a glypican-3 (GPC3) peptide vaccine in patients with advanced hepatocellular carcinoma (HCC); however, its immunological mechanism of action remains unclear. Here, we report a pilot study conducted to evaluate the immunological mechanisms of action of this GPC3 peptide vaccine (UMIN-CTR number 000005093). Eleven patients with advanced HCC were vaccinated with the GPC3 peptide in this trial. The primary end point was GPC3 peptide-specific immune response induced by the GPC3 peptide vaccination...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/29123947/translational-nanoparticle-engineering-for-cancer-vaccines
#20
REVIEW
Adam J Grippin, Elias J Sayour, Duane A Mitchell
Conventional cancer treatments remain insufficient to treat many therapy-resistant tumors.(1) Cancer vaccines attempt to overcome this resistance by activating the patient's immune system to eliminate tumor cells without the toxicity of systemic chemotherapy and radiation. Nanoparticles (NPs) are promising as customizable, immunostimulatory carriers to protect and deliver antigen. Although many NP vaccines have been investigated in preclinical settings, a few have advanced into clinical application, and still fewer have demonstrated clinical benefit...
2017: Oncoimmunology
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