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Immune engineering

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https://www.readbyqxmd.com/read/28543738/crispr-editing-in-biological-and-biomedical-investigation
#1
Xing-Da Ju, Jing Xu, Zhong Sheng Sun
The CRISPR (clustered regularly interspaced short palindromic repeat)-Cas (CRISPR--associated protein) system, a prokaryotic RNA-based adaptive immune system against viral infection, is emerging as a powerful genome editing tool in broad research areas. To further improve and expand its functionality, various CRISPR delivery strategies have been tested and optimized, and key CRISPR system components such as Cas protein have been engineered with different purposes. Benefiting from more in-depth understanding and further development of CRISPR, versatile CRISPR-based platforms for genome editing have been rapidly developed to advance investigations in biology and biomedicine...
May 20, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28542609/potent-and-selective-inhibition-of-pathogenic-viruses-by-engineered-ubiquitin-variants
#2
Wei Zhang, Ben A Bailey-Elkin, Robert C M Knaap, Baldeep Khare, Tim J Dalebout, Garrett G Johnson, Puck B van Kasteren, Nigel J McLeish, Jun Gu, Wenguang He, Marjolein Kikkert, Brian L Mark, Sachdev S Sidhu
The recent Middle East respiratory syndrome coronavirus (MERS-CoV), Ebola and Zika virus outbreaks exemplify the continued threat of (re-)emerging viruses to human health, and our inability to rapidly develop effective therapeutic countermeasures. Many viruses, including MERS-CoV and the Crimean-Congo hemorrhagic fever virus (CCHFV) encode deubiquitinating (DUB) enzymes that are critical for viral replication and pathogenicity. They bind and remove ubiquitin (Ub) and interferon stimulated gene 15 (ISG15) from cellular proteins to suppress host antiviral innate immune responses...
May 18, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28542462/a-human-monocytic-nf-%C3%AE%C2%BAb-fluorescent-reporter-cell-line-for-detection-of-microbial-contaminants-in-biological-samples
#3
Claire Battin, Annika Hennig, Patrick Mayrhofer, Renate Kunert, Gerhard J Zlabinger, Peter Steinberger, Wolfgang Paster
Sensing of pathogens by innate immune cells is essential for the initiation of appropriate immune responses. Toll-like receptors (TLRs), which are highly sensitive for various structurally and evolutionary conserved molecules derived from microbes have a prominent role in this process. TLR engagement results in the activation of the transcription factor NF-κB, which induces the expression of cytokines and other inflammatory mediators. The exquisite sensitivity of TLR signalling can be exploited for the detection of bacteria and microbial contaminants in tissue cultures and in protein preparations...
2017: PloS One
https://www.readbyqxmd.com/read/28539557/prospects-for-personalized-combination-immunotherapy-for-solid-tumors-based-on-adoptive-cell-therapies-and-immune-checkpoint-blockade-therapies
#4
Daiki Kato, Tomonori Yaguchi, Takashi Iwata, Kenji Morii, Takayuki Nakagawa, Ryohei Nishimura, Yutaka Kawakami
  Immune checkpoint blockade (ICB) and adoptive cell therapies (ACT) with antigen-receptor gene-engineered T cells have been shown to be successful for a limited number of patients with solid tumors. Responders to ICB therapy typically have T cell-inflamed tumors. Thus, it is important to develop strategies that convert non-T cell-inflamed tumors to T cell-inflamed tumors. Although chimeric antigen receptor transduced T (CAR-T) cell therapy targeting hematological malignancies demonstrated durable clinical responses, the success of gene-engineered T cell therapies in solid tumors is hampered by a lack of unique antigens, antigen loss in cancer cells, and the immune-suppressive tumor microenvironment (TME) of solid tumors...
2017: Nihon Rinshō Men'eki Gakkai Kaishi, Japanese Journal of Clinical Immunology
https://www.readbyqxmd.com/read/28538671/engineering-exosomes-for-cancer-therapy
#5
REVIEW
Katie E Gilligan, Róisín M Dwyer
There remains an urgent need for novel therapeutic strategies to treat metastatic cancer, which results in over 8 million deaths annually worldwide. Following secretion, exosomes are naturally taken up by cells, and capable of the stable transfer of drugs, therapeutic microRNAs and proteins. As knowledge of the biogenesis, release and uptake of exosomes continues to evolve, and thus also has interest in these extracellular vesicles as potential tumor-targeted vehicles for cancer therapy. The ability to engineer exosome content and migratory itinerary holds tremendous promise...
May 24, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28536890/progress-and-future-prospectives-in-skin-on-chip-development-with-emphasis-on-the-use-of-different-cell-types-and-technical-challenges
#6
Lenie J van den Broek, Lambert I J C Bergers, Christianne M A Reijnders, Susan Gibbs
Understanding the healthy and diseased state of skin is important in many areas of basic and applied research. Although the field of skin tissue engineering has advanced greatly over the last years, current in vitro skin models still do not mimic the complexity of the human skin. Skin-on-chip and induced pluripotent stem cells (iPSC) might be key technologies to improve in vitro skin models. This review summarizes the state of the art of in vitro skin models with regard to cell sources (primary, cell line, iPSC) and microfluidic devices...
May 24, 2017: Stem Cell Reviews
https://www.readbyqxmd.com/read/28536562/use-of-wild-type-or-recombinant-lactic-acid-bacteria-as-an-alternative-treatment-for-gastrointestinal-inflammatory-diseases-a-focus-on-inflammatory-bowel-diseases-and-mucositis
#7
REVIEW
Rodrigo D De Oliveira Carvalho, Fillipe L R do Carmo, Alberto de Oliveira Junior, Philippe Langella, Jean-Marc Chatel, Luis G Bermúdez-Humarán, Vasco Azevedo, Marcela S de Azevedo
The human gastrointestinal tract (GIT) is highly colonized by bacterial communities, which live in a symbiotic relationship with the host in normal conditions. It has been shown that a dysfunctional interaction between the intestinal microbiota and the host immune system, known as dysbiosis, is a very important factor responsible for the development of different inflammatory conditions of the GIT, such as the idiopathic inflammatory bowel diseases (IBD), a complex and multifactorial disorder of the GIT. Dysbiosis has also been implicated in the pathogenesis of other GIT inflammatory diseases such as mucositis usually caused as an adverse effect of chemotherapy...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28536388/capitalizing-on-cancer-specific-replication-oncolytic-viruses-as-a-versatile-platform-for-the-enhancement-of-cancer-immunotherapy-strategies
#8
REVIEW
Donald Bastin, Scott R Walsh, Meena Al Saigh, Yonghong Wan
The past decade has seen considerable excitement in the use of biological therapies in treating neoplastic disease. In particular, cancer immunotherapy and oncolytic virotherapy have emerged as two frontrunners in this regard with the first FDA approvals for agents in both categories being obtained in the last 5 years. It is becoming increasingly apparent that these two approaches are not mutually exclusive and that much of the therapeutic benefit obtained from the use of oncolytic viruses (OVs) is in fact the result of their immunotherapeutic function...
August 24, 2016: Biomedicines
https://www.readbyqxmd.com/read/28536386/recombinant-poxvirus-and-the-tumor-microenvironment-oncolysis-immune-regulation-and-immunization
#9
REVIEW
Daniel W Sharp, Edmund C Lattime
Oncolytic viruses (OVs) are being extensively studied for their potential roles in the development of cancer therapy regimens. In addition to their direct lytic effects, OVs can initiate and drive systemic antitumor immunity indirectly via release of tumor antigen, as well as by encoding and delivering immunostimulatory molecules. This combination makes them an effective platform for the development of immunotherapeutic strategies beyond their primary lytic function. Engineering the viruses to also express tumor-associated antigens (TAAs) allows them to simultaneously serve as therapeutic vaccines, targeting and amplifying an immune response to TAAs...
August 12, 2016: Biomedicines
https://www.readbyqxmd.com/read/28536346/taking-a-stab-at-cancer-oncolytic-virus-mediated-anti-cancer-vaccination-strategies
#10
REVIEW
Amelia Sadie Aitken, Dominic Guy Roy, Marie-Claude Bourgeois-Daigneault
Vaccines have classically been used for disease prevention. Modern clinical vaccines are continuously being developed for both traditional use as well as for new applications. Typically thought of in terms of infectious disease control, vaccination approaches can alternatively be adapted as a cancer therapy. Vaccines targeting cancer antigens can be used to induce anti-tumour immunity and have demonstrated therapeutic efficacy both pre-clinically and clinically. Various approaches now exist and further establish the tremendous potential and adaptability of anti-cancer vaccination...
January 4, 2017: Biomedicines
https://www.readbyqxmd.com/read/28536345/viroimmunotherapy-of-thoracic-cancers
#11
REVIEW
Alexander S Dash, Manish R Patel
Thoracic cancers, including non-small cell lung cancer (NSCLC), small cell lung cancer (SCLC), and malignant pleural mesothelioma (MM), cause the highest rate of cancer mortality worldwide. Most of these deaths are as a result of NSCLC; however, prognoses for the other two diseases remain as some of the poorest of any cancers. Recent advances in immunotherapy, specifically immune checkpoint inhibitors, have begun to help a small population of patients with advanced lung cancer. People who respond to these immune therapies generally have a durable response and many see dramatic decreases in their disease...
January 4, 2017: Biomedicines
https://www.readbyqxmd.com/read/28536278/immune-checkpoint-blockade-immunogenic-chemotherapy-or-ifn-%C3%AE-blockade-boost-the-local-and-abscopal-effects-of-oncolytic-virotherapy
#12
Laetitia Fend, Takahiro Yamazaki, Christelle Remy, Catherine Fahrner, Murielle Gantzer, Virginie Nourtier, Xavier Préville, Eric Quéméneur, Oliver Kepp, Julien Adam, Aurélien Marabelle, Jonathan M Pitt, Guido Kroemer, Laurence Zitvogel
Athough the clinical efficacy of oncolytic viruses has been demonstrated for local treatment, the ability to induce immune-mediated regression of distant metastases is still poorly documented. We report here that the engineered oncolytic vaccinia virus VVWR-TK(-)RR(-)-Fcu1 can induce immunogenic cell death and generate a systemic immune response. Effects on tumor growth and survival was largely driven by CD8(+) T cells, and immune cell infiltrate in the tumor could be reprogrammed towards a higher ratio of effector T cells to regulatory CD4(+) T cells...
May 23, 2017: Cancer Research
https://www.readbyqxmd.com/read/28534085/atp-induced-ca-2-signalling-mechanisms-in-the-regulation-of-mesenchymal-stem-cell-migration
#13
REVIEW
Lin-Hua Jiang, Fatema Mousawi, Xuebin Yang, Sėbastien Roger
The ability of cells to migrate to the destined tissues or lesions is crucial for physiological processes from tissue morphogenesis, homeostasis and immune responses, and also for stem cell-based regenerative medicines. Cytosolic Ca(2+) is a primary second messenger in the control and regulation of a wide range of cell functions including cell migration. Extracellular ATP, together with the cognate receptors on the cell surface, ligand-gated ion channel P2X receptors and a subset of G-protein-coupled P2Y receptors, represents common autocrine and/or paracrine Ca(2+) signalling mechanisms...
May 22, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/28533272/chimeric-pd-1-28-receptor-upgrades-low-avidity-t-cells-and-restores-effector-function-of-tumor-infiltrating-lymphocytes-for-adoptive-cell-therapy
#14
Ramona Schlenker, Luis Felipe Olguín-Contreras, Matthias Leisegang, Julia Schnappinger, Anja Disovic, Svenja Rühland, Peter J Nelson, Heinrich Leonhardt, Hartmann Harz, Susanne Wilde, Dolores J Schendel, Wolfgang Uckert, Gerald Willimsky, Elfriede Noessner
Inherent intermediate-to-low affinity T cell receptors (TCR) that develop during the natural course of immune responses may not allow sufficient activation for tumor elimination, making the majority of T cells suboptimal for adoptive T cell therapy (ATT). TCR affinity enhancement has been implemented to provide stronger T cell activity but carries the risk of creating undesired cross-reactivity leading to potential serious adverse effects in clinical application. We demonstrate here that engineering of low-avidity T cells recognizing a naturally processed and presented tumor-associated antigen with a chimeric PD-1:28 receptor increases effector function to levels seen with high-avidity T cells of identical specificity...
May 22, 2017: Cancer Research
https://www.readbyqxmd.com/read/28532790/a-safe-and-molecular-tagged-brucella-canis-ghosts-confers-protection-against-virulent-challenge-in-mice
#15
Jing Qian, Zhaoyang Bu, Xulong Lang, Guangmou Yan, Yanling Yang, Xiuran Wang, Xinglong Wang
Canine brucellosis, caused by Brucella canis, is a persistent infectious reproductive disease in dogs. The absence of effective treatment to the intracellular pathogen and the irreversible consequence of infection makes the need of a specific vaccine urgent. Bacterial ghosts (BGs) are the empty envelopes of bacteria with no genome content inside, which emerge as a proper vaccine candidate due to its intact outer antigen. It is generally derived from a genetically engineered strain, through the expression of Bacteriophage phiX174 lysis E gene upon induction...
May 2017: Veterinary Microbiology
https://www.readbyqxmd.com/read/28532690/combinatorial-drug-delivery-approaches-for-immunomodulation
#16
Joshua M Stewart, Benjamin G Keselowsky
Immunotherapy has been widely explored for applications to both augment or suppress intrinsic host immunity. Clinical achievements have seen a number of immunotherapeutic drugs displace established strategies like chemotherapy in treating immune-associated diseases. However, single drug approaches modulating an individual arm of the immune system are often incompletely effective. Imperfect mechanistic understanding and heterogeneity within disease pathology have seen monotherapies inadequately equipped to mediate complete disease remission...
May 19, 2017: Advanced Drug Delivery Reviews
https://www.readbyqxmd.com/read/28532102/islet-encapsulated-implantable-composite-hollow-fiber-membrane-based-device-a-bioartificial-pancreas
#17
Rohit S Teotia, Sachin Kadam, Atul Kumar Singh, Surendra Kumar Verma, Ashutosh Bahulekar, Sujata Kanetkar, Jayesh Bellare
Islets from xeno-sources and islet like clusters derived from autologus stem cells have emerged as alternatives to cadaveric pancreas used for treatment of type 1 diabetes. However, the immuno-isolation of these islets from the host immune system suffers from the issue of biocompatibility and hypoxia. To overcome the issues of immunobarrier biocompatibility, we developed a Polysulfone (Psf)/TPGS composite hollow fiber membrane (HFM) using a hollow fiber spinning pilot plant specially developed for this purpose...
August 1, 2017: Materials Science & Engineering. C, Materials for Biological Applications
https://www.readbyqxmd.com/read/28531117/immunobiology-of-newcastle-disease-virus-and-its-use-for-prophylactic-vaccination-in-poultry-and-as-adjuvant-for-therapeutic-vaccination-in-cancer-patients
#18
REVIEW
Volker Schirrmacher
Newcastle disease (ND) is one of the most important diseases of poultry worldwide. In the last decades, molecular research has gained a lot of new information about its causative agent, newcastledisease virus (NDV). In poultry industry, certain strains of NDV have been used for preventive vaccination for more than 60 years. NDV has also been applied to cancer patients with beneficial effects for about 50 years, but this is less well known. The molecular basis for these differential effects of NDV in birds and man have been elucidated in the last decades and are explained in this review...
May 20, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28530164/biocompatibility-of-intensified-decellularized-equine-carotid-arteries-in-a-rat-subcutaneous-implantation-model-and-in-a-human-in-vitro-model
#19
Niklas Jeinsen, Lavinia Maegel, Danny Jonigk, Melanie Klingenberg, Axel Haverich, Mathias Wilhelmi, Ulrike Böer
Limited biocompatibility of decellularized scaffolds is an ongoing challenge in tissue engineering. We recently demonstrated that intensified detergent-based decellularization of equine carotid artery (dEACintens) removed residual cellular molecules from the scaffold more efficiently than a conventional decellularization (dEACcon) though this approach did not eliminate its immunogenicity entirely. CCN1 has been shown to improve biocompatibility of dEACcon in a sheep model. Here, we tested the biocompatibility of dEACintens and dEACcon with or without CCN1-coating after subcutaneous implantation in rats for up to 12 weeks...
May 20, 2017: Tissue Engineering. Part A
https://www.readbyqxmd.com/read/28529904/mini-review-of-conventional-and-hypofractionated-radiation-therapy-combined-with-immunotherapy-for-non-small-cell-lung-cancer
#20
REVIEW
Allison M Campbell, Roy H Decker
A successful antitumoral response requires immunological activation as well as an antigenic pool capable of stimulating both the innate and the adaptive immune system. Recent advances in immunotherapy have been aimed at boosting the activation status of the innate and adaptive immune system, including cytokine administration, monoclonal antibodies engineered to target high yield elements in oncogenic signaling pathways, cancer vaccines, and checkpoint inhibitors. Herein, we examine the ways that radiation therapy induced cell death provides a pool of stimulus antigen, and draw parallels from the immunobiology of autoimmunity to explore how the immunogenicity of antigen derived from radiation-induced cell death might augment the antitumoral response...
April 2017: Translational Lung Cancer Research
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