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Engineered immune cells

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https://www.readbyqxmd.com/read/28334154/ethical-issues-of-crispr-technology-and-gene-editing-through-the-lens-of-solidarity
#1
John J Mulvihill, Benjamin Capps, Yann Joly, Tamra Lysaght, Hub A E Zwart, Ruth Chadwick
Background: The avalanche of commentaries on CRISPR-Cas9 technology, a bacterial immune system modified to recognize any short DNA sequence, cut it out, and insert a new one, has rekindled hopes for gene therapy and other applications and raised criticisms of engineering genes in future generations. Sources of data: This discussion draws on articles that emphasize ethics, identified partly through PubMed and Google, 2014-2016. Areas of agreement: CRISPR-Cas9 has taken the pace and prospects for genetic discovery and applications to a high level, stoking anticipation for somatic gene engineering to help patients...
February 23, 2017: British Medical Bulletin
https://www.readbyqxmd.com/read/28332231/development-of-humanized-mice-in-the-age-of-genome-editing
#2
Vishnu Hosur, Benjamin E Low, Cindy Avery, Leonard D Shultz, Michael V Wiles
Mice are the most commonly used model organisms to study human disease. Many genetic human diseases can be recapitulated by modifying the mouse genome, which permits testing of existing and novel therapeutics, including combinatorial therapeutics, without putting humans at risk. Specifically, the development of "humanized" mice, i.e., severely immunodeficient mice engrafted with functional human hematopoietic and immune cells and tissues, has revolutionized our ability to study and model human diseases in preclinical in vivo systems...
March 22, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28332200/immunoregulation-of-inflammatory-and-inhibitory-cytokines-by-vitamin-d3-in-patients-with-inflammatory-bowel-diseases-ibd
#3
REVIEW
Hussaini Mohammed Alhassan, Abbas Mirshafiey, Homayoun Vahedi, Gholamreza Hemmasi, Ateke Moussavi Nasl Khameneh, Karim Parastouei, Ali Akbar Saboor-Yaraghi
Inflammatory bowel disease (IBD) is a group of idiopathic, chronic and relapsing inflammatory conditions of the gastrointestinal tract, caused by an aberrant and exaggerated immunological response in the gut. Supplementation of Vitamin D3 in IBD patients exerts both direct and indirect regulatory roles on the naïve T-cells, thereby maintaining a balance between inflammatory and inhibitory cytokines. The direct actions of Vitamin D3 on naïve T-cells result in the proliferation of more regulatory T-cells and inhibitory cytokines such as IL-4, IL-10, and IL-5...
March 22, 2017: Scandinavian Journal of Immunology
https://www.readbyqxmd.com/read/28330372/car-t-cell-therapy-progress-and-prospects
#4
Olivia Wilkins, Allison May Keeler, Terence R Flotte
Lentivirus-mediated transduction of autologous T-cells with a chimeric antigen receptor (CAR) to confer a desired epitope-specificity as a targeted immunotherapy for cancer has been among the first human gene therapy techniques to demonstrate widespread therapeutic efficacy. Other approaches to using gene therapy to enhance anti-tumor immunity have been less specific and less effective. These included amplification, marking, and cytokine transduction of tumor infiltrating lymphocytes (TIL), recombinant virus-based expression of tumor antigens as a tumor vaccine, and transduction of antigen-presenting cells (APCs) with tumor antigens...
March 23, 2017: Human Gene Therapy Methods
https://www.readbyqxmd.com/read/28323411/engineering-an-injectable-muscle-specific-microenvironment-for-improved-cell-delivery-using-a-nanofibrous-extracellular-matrix-hydrogel
#5
Nikhil Rao, Gillie Agmon, Matthew T Tierney, Jessica L Ungerleider, Rebecca L Braden, Alessandra Sacco, Karen L Christman
Injection of skeletal muscle progenitors has the potential to be a minimally invasive treatment for a number of diseases that negatively affect vasculature and skeletal muscle, including peripheral artery disease (PAD). However, success with this approach has been limited because of poor transplant cell survival. This is primarily attributed to cell death due to extensional flow through the needle, the harsh ischemic environment of the host tissue, a deleterious immune cell response, and a lack of biophysical cues supporting exogenous cell viability...
March 21, 2017: ACS Nano
https://www.readbyqxmd.com/read/28322923/microspheres-prime-rmva-boost-vaccination-enhances-humoral-and-cellular-immune-response-in-ifnar-mice-conferring-protection-against-serotypes-1-and-4-of-bluetongue-virus
#6
Alejandro Marín-López, Eva Calvo-Pinilla, Diego Barriales, Gema Lorenzo, Javier Benavente, Alejandro Brun, Jose Manuel Martínez-Costas, Javier Ortego
Bluetongue virus (BTV) is the causative agent of bluetongue disease (BT), which affects domestic and wild ruminants. At the present, 27 different serotypes have been documented. Vaccination has been demonstrated as one of the most effective methods to avoid viral dissemination. To overcome the drawbacks associated with the use of inactivated and attenuated vaccines we engineered a new recombinant BTV vaccine candidate based on proteins VP2, VP7, and NS1 of BTV-4 that were incorporated into avian reovirus muNS-Mi microspheres (MS-VP2/VP7/NS1) and recombinant modified vaccinia virus Ankara (rMVA)...
March 16, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28322797/transcriptional-activation-of-the-mica-gene-with-an-engineered-crispr-cas9-system
#7
Kazuma Sekiba, Mari Yamagami, Motoyuki Otsuka, Tatsunori Suzuki, Takahiro Kishikawa, Rei Ishibashi, Motoko Ohno, Masaya Sato, Kazuhiko Koike
Major histocompatibility complex class I polypeptide-related sequence A (MICA) is a prototypical NKG2D ligand. Because immune cells, such as natural killer (NK) cells, recognize virally infected or transformed cells and eliminate them through the interaction between NKG2D receptors on NK cells and NKG2D ligands on pathogenic cells, MICA expression levels are associated with NK cell-mediated immunity. Here, we report that an engineered clustered regularly interspaced short palindromic repeats-Cas9-related complex targeting MICA gene promoter sequences activates transcription of the MICA gene from its endogenous locus...
March 18, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28322169/potential-therapeutic-strategies-of-regenerative-medicine-for-renal-failure
#8
Monica Maribel Mata-Miranda, Raul Jacobo Delgado-Macuil, Marlon Rojas-Lopez, Ricardo Martinez-Flores, Gustavo Jesus Vazquez-Zapien
Kidney diseases are a public health problem worldwide; the mortality rate is between 50 and 80%. Available therapies include replacement function by dialysis or transplant, associated with a high morbidity and mortality; kidney transplantation is limited by the shortage of donor organs, immune rejection and lifelong treatment with immunosuppressive. Likewise, none of these treatments compensates all kidney functions. There is a great concern in developing more effective therapies with the ability to replace the wide range of renal functions, so that, new researches on developing therapeutic strategies have focused on regenerative medicine, science that includes artificial creation of tissues and organs, in order to repair or replace a tissue or organ function...
March 17, 2017: Current Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28318643/cxcl10-alters-the-tumour-immune-microenvironment-and-disease-progression-in-a-syngeneic-murine-model-of-high-grade-serous-ovarian-cancer
#9
Katrina K Au, Nichole Peterson, Peter Truesdell, Gillian Reid-Schachter, Kasra Khalaj, Runhan Ren, Julie-Ann Francis, Charles H Graham, Andrew W Craig, Madhuri Koti
OBJECTIVE: We recently established that high STAT1 expression and associated T helper type I tumour immune microenvironment (TME) are prognostic and chemotherapy response predictive biomarkers in high-grade serous ovarian cancer (HGSC). STAT1 induced chemokine CXCL10 is key to the recruitment of lymphocytes in the TME and is significantly highly expressed in the tumours from patients with longer survival. In the current study we therefore aimed to elucidate the role CXCL10 in disease progression and tumour immune transcriptomic alterations using the ID8 syngeneic murine model of HGSC...
March 16, 2017: Gynecologic Oncology
https://www.readbyqxmd.com/read/28317440/potent-immune-responses-induced-by-a-salmonella-ghost-delivery-system-that-expresses-the-recombinant-stx2eb-fedf-and-feda-proteins-of-the-escherichia-coli-producing-f18-and-shiga-toxin-in-a-murine-model-and-evaluation-of-its-protective-effect-as-a-porcine-vaccine
#10
Gayeon Won, John Hwa Lee
BACKGROUND: In the pathogenicity of porcine edema disease, which is caused by the Escherichia coli-producing F18 and Shiga toxin, F18(+) fimbrial adhesins and Shiga toxin 2e (Stx2e) play pivotal roles in the colonization and enterotoxicity of this pathogen. OBJECTIVE: To develop a vaccine candidate against edema disease by combining three selected antigens of F18(+) Shiga toxin-producing Escherichia coli (STEC). METHODS: Genetically engineered Salmonella Typhimurium (ST) ghosts that express Stx2eB, FedF, and FedA were individually inserted in a ghost plasmid cassette (pJHL184), and the resultant plasmids were transformed into a Δasd Δlon ΔcpxR ST (JOL912)...
March 20, 2017: Veterinary Quarterly
https://www.readbyqxmd.com/read/28316596/the-efficacy-of-humanized-antibody-against-the-sporothrix-antigen-gp70-in-promoting-phagocytosis-and-reducing-disease-burden
#11
José R F de Almeida, Karla L Santiago, Gilberto H Kaihami, Andrea Q Maranhão, Marcelo de Macedo Brígido, Sandro R de Almeida
Sporotrichosis is a subcutaneous mycosis distributed worldwide and is frequently reported in countries with tropical climates, as Latin America countries. We previously demonstrated that mice with sporotrichosis produce specific antibodies against a 70-kDa fungal protein, indicating that specific antibodies against this molecule may help to control the sporotrichosis. IgG1 monoclonal antibody was generated, and called mAbP6E7, in mice against a 70-kDa glycoprotein (gp70) of S. schenckii. The mAbP6E7 showed prophylactic and therapeutic activity against sporotrichosis...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28315359/antibodies-and-associates-partners-in-targeted-drug-delivery
#12
REVIEW
Patrick J Kennedy, Carla Oliveira, Pedro L Granja, Bruno Sarmento
Monoclonal antibodies (mAbs) are well established in the clinic due to their specificity and affinity to a diverse array of biochemical targets. More recently, mAbs are being exploited as targeting agents in modern drug delivery systems, aiming to bypass normal host tissue and to accumulate a therapeutic agent to a specific tissue or cell for enhanced pharmacology. At sizes ranging from ~10-100nm, antibody-based bioconjugates have opened up a whole new realm of clinical possibilities with several platforms emerging on the market...
March 14, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28314377/the-effects-of-scaffold-remnants-in-decellularized-tissue-engineered-cardiovascular-constructs-on-the-recruitment-of-blood-cells
#13
Bart Sanders, Anita Driessen-Mol, Carlijn Bouten, Frank Baaijens
Decellularized tissue engineered heart valves (DTEHVs) showed remarkable results in translational animal models, leading to recellularization within hours after implantation. This is crucial to enable tissue remodeling. To investigate if the presence of scaffold remnants prior to implantation is responsible for the fast recellularization of DTEHVs, an in vitro mesofluidic system was used. Human granulocyte and agranulocyte fractions were isolated, stained, brought back in suspension, and implemented in the system...
March 17, 2017: Tissue Engineering. Part A
https://www.readbyqxmd.com/read/28302645/pd-l1-on-tumor-cells-is-sufficient-for-immune-evasion-in-immunogenic-tumors-and-inhibits-cd8-t-cell-cytotoxicity
#14
Vikram R Juneja, Kathleen A McGuire, Robert T Manguso, Martin W LaFleur, Natalie Collins, W Nicholas Haining, Gordon J Freeman, Arlene H Sharpe
It is unclear whether PD-L1 on tumor cells is sufficient for tumor immune evasion or simply correlates with an inflamed tumor microenvironment. We used three mouse tumor models sensitive to PD-1 blockade to evaluate the significance of PD-L1 on tumor versus nontumor cells. PD-L1 on nontumor cells is critical for inhibiting antitumor immunity in B16 melanoma and a genetically engineered melanoma. In contrast, PD-L1 on MC38 colorectal adenocarcinoma cells is sufficient to suppress antitumor immunity, as deletion of PD-L1 on highly immunogenic MC38 tumor cells allows effective antitumor immunity...
March 16, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28297677/recombinant-bcg-expressing-esx-1-of-mycobacterium-marinum-combines-low-virulence-with-cytosolic-immune-signaling-and-improved-tb-protection
#15
Matthias I Gröschel, Fadel Sayes, Sung Jae Shin, Wafa Frigui, Alexandre Pawlik, Mickael Orgeur, Robin Canetti, Nadine Honoré, Roxane Simeone, Tjip S van der Werf, Wilbert Bitter, Sang-Nae Cho, Laleh Majlessi, Roland Brosch
Recent insights into the mechanisms by which Mycobacterium tuberculosis, the etiologic agent of human tuberculosis, is recognized by cytosolic nucleotide sensors have opened new avenues for rational vaccine design. The only licensed anti-tuberculosis vaccine, Mycobacterium bovis BCG, provides limited protection. A feature of BCG is the partial deletion of the ESX-1 type VII secretion system, which governs phagosomal rupture and cytosolic pattern recognition, key intracellular phenotypes linked to increased immune signaling...
March 14, 2017: Cell Reports
https://www.readbyqxmd.com/read/28296287/bio-inspired-nanomedicine-strategies-for-artificial-blood-components
#16
REVIEW
Anirban Sen Gupta
Blood is a fluid connective tissue where living cells are suspended in noncellular liquid matrix. The cellular components of blood render gas exchange (RBCs), immune surveillance (WBCs) and hemostatic responses (platelets), and the noncellular components (salts, proteins, etc.) provide nutrition to various tissues in the body. Dysfunction and deficiencies in these blood components can lead to significant tissue morbidity and mortality. Consequently, transfusion of whole blood or its components is a clinical mainstay in the management of trauma, surgery, myelosuppression, and congenital blood disorders...
March 15, 2017: Wiley Interdisciplinary Reviews. Nanomedicine and Nanobiotechnology
https://www.readbyqxmd.com/read/28294555/promise-and-peril-in-nanomedicine-the-challenges-and-needs-for-integrated-systems-biology-approaches-to-define-health-risk
#17
REVIEW
Sabina Halappanavar, Ulla Vogel, Hakan Wallin, Carole L Yauk
In the 1966s visionary film 'Fantastic Voyage' a submarine crew was shrunk to 100 nm in size and injected into the body of an injured scientist to repair his damaged brain. The movie (written by Harry Kleiner; directed by Richard Fleischer; novel by Isaac Asimov) drew attention to the potential power of engineered nanoscale structures and devices to construct, monitor, control, treat, and repair individual cells. Even more interesting was the fact that the film elegantly noted that the structure had to be miniaturized to a size that is not detected by the body's immune surveillance system, and highlighted the many physiological barriers that are encountered on the submarine's long journey to the target...
March 15, 2017: Wiley Interdisciplinary Reviews. Nanomedicine and Nanobiotechnology
https://www.readbyqxmd.com/read/28294424/therapeutic-regulation-of-systemic-inflammation-in-xenograft-recipients
#18
Hayato Iwase, Hong Liu, Tao Li, Zhongquiang Zhang, Bingsi Gao, Hidetaka Hara, Martin Wijkstrom, Cassandra Long, Ryan Saari, David Ayares, David K C Cooper, Mohamed B Ezzelarab
Inflammation is known to preclude tolerance after transplantation. We have previously shown that systemic inflammation in xenograft recipients (SIXR) precedes activation of coagulation in the absence of T cell responses. Accordingly, SIXR may amplify innate and adaptive immune responses against xenografts after pig-to-primate xenotransplantation, even with efficient immunosuppressive therapy. We evaluated the impact of anti-inflammatory agents on pro-inflammatory cytokines and chemokines in pig artery patch and heart xenograft recipients...
March 12, 2017: Xenotransplantation
https://www.readbyqxmd.com/read/28293795/a-workflow-for-in-silico-design-of-hil-10-and-ebvil-10-inhibitors-using-well-known-miniprotein-scaffolds
#19
Salvador Dueñas, Sergio A Aguila, Genaro Pimienta
The over-expression of immune-suppressors such as IL-10 is a crucial landmark in both tumor progression, and latent viral and parasite infection. IL-10 is a multifunctional protein. Besides its immune-cell suppressive function, it also promotes B-cell tumorigenesis of lymphomas and melanoma. Human pathogens like unicellular parasites and viruses that remain latent inside B cells promote the over-expression of hIL-10 upon infection, which inhibits cell-mediated immune surveillance, and at the same time mediates B cell proliferation...
April 2017: Journal of Molecular Modeling
https://www.readbyqxmd.com/read/28287876/crispr-cas9-from-a-bacterial-immune-system-to-genome-edited-human-cells-in-clinical-trials
#20
Leonhard Kick, Marion Kirchner, Sabine Schneider
The adaptive bacterial immune system CRISPR-Cas is revolutionising all fields of life science and has opened up new frontiers towards personalised medicine. Since the elucidation of the molecular mechanism of Cas9 from Streptococcus pyogenes in 2012 and its development as a genomic engineering tool, genetic modifications in more than 40 species have been carried out, over 290 patents have been filed worldwide and the first clinical trials using CRISPR-Cas-modified T-cells have recently been started in China and in the US...
March 13, 2017: Bioengineered
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