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Engineered immune cells

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https://www.readbyqxmd.com/read/27926545/immune-responses-to-bioengineered-organs
#1
Jordi Ochando, Dominique Charron, Pedro M Baptista, Basak E Uygun
PURPOSE OF REVIEW: Organ donation in the United States registered 9079 deceased organ donors in 2015. This high percentage of donations allowed organ transplantation in 29 851 recipients. Despite increasing numbers of transplants performed in comparison with previous years, the numbers of patients that are in need for a transplant increase every year at a higher rate. This reveals that the discrepancy between the demand and availability of organs remains fundamental problem in organ transplantation...
December 6, 2016: Current Opinion in Organ Transplantation
https://www.readbyqxmd.com/read/27919783/the-potential-of-induced-pluripotent-stem-cells-as-a-tool-to-study-skeletal-dysplasias-and-cartilage-related-pathologic-conditions
#2
REVIEW
Huan Liu, Lei Yang, Fang Fang Yu, Sen Wang, Cuiyan Wu, Chengjuan Qu, Xiong Guo, Mikko J Lammi
The development of induced pluripotent stem cells (iPSCs) technology has opened up new horizons for development of new research tools especially for skeletal dysplasias, which often lack human disease models. Regenerative medicine and tissue engineering could be the next areas to benefit from refinement of iPSC methods to repair focal cartilage defects, while applications for osteoarthritis (OA) and drug screening have evolved rather slowly. Although the advances in iPSC research of skeletal dysplasias and repair of focal cartilage lesions are not directly relevant to OA, they can be considered to pave the way to future prospects and solutions to OA research, too...
December 2, 2016: Osteoarthritis and Cartilage
https://www.readbyqxmd.com/read/27917363/future-therapy-for-hepatitis-b-virus-role-of-immunomodulators
#3
REVIEW
Edward A Pham, Ryan B Perumpail, Benjamin J Fram, Jeffrey S Glenn, Aijaz Ahmed, Robert G Gish
Although currently available therapies for chronic hepatitis B virus infection can suppress viremia and provide long-term benefits for patients, they do not lead to a functional cure for most patients. Advances in our understanding of the virus-host interaction and the recent remarkable success of immunotherapy in cancer offer new and promising strategies for developing immune modulators that may become important components of a total therapeutic approach to hepatitis B, some of which are now in clinical development...
2016: Current Hepatology Reports
https://www.readbyqxmd.com/read/27914464/immunogenicity-of-human-interferon-beta-containing-pharmaceuticals
#4
V D Nazarov, S V Lapin, A V Mazing, E P Evdoshenko, A A Totolian
Multiple sclerosis is a severe autoimmune disease with inflammatory component that continues to be resistant to treatment. One of the approaches retarding its progression is based on using nonspecific therapy with human interferon-beta (IFN-β)-containing pharmaceuticals. Neutralizing antibodies (NAbs) against genetically engineered pharmaceuticals developed by the patient's immune system, which reduce their therapeutic and biological activity, pose a serious problem. Cell lines sensitive to IFN-β activity also quantifying NAb level are applied because direct measurement of IFN-β antiviral activity is complicated...
November 2016: Biochemistry. Biokhimii︠a︡
https://www.readbyqxmd.com/read/27914063/episweep-computationally-driven-reengineering-of-therapeutic-proteins-to-reduce-immunogenicity-while-maintaining-function
#5
Yoonjoo Choi, Deeptak Verma, Karl E Griswold, Chris Bailey-Kellogg
Therapeutic proteins are yielding ever more advanced and efficacious new drugs, but the biological origins of these highly effective therapeutics render them subject to immune surveillance within the patient's body. When recognized by the immune system as a foreign agent, protein drugs elicit a coordinated response that can manifest a range of clinical complications including rapid drug clearance, loss of functionality and efficacy, delayed infusion-like allergic reactions, more serious anaphylactic shock, and even induced auto-immunity...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27913524/cellular-and-vaccine-immunotherapy-for-multiple-myeloma
#6
Alfred L Garfall, Edward A Stadtmauer
Allogeneic hematopoietic cell transplantation and donor lymphocyte infusion for multiple myeloma (MM) can induce graft-versus-myeloma immunity and long-term survivorship, but limited efficacy and associated toxicities have prevented its widespread use. Cellular immunotherapies and vaccines seek to induce more specific, reliable, and potent antimyeloma immune responses with less treatment-related risk than is possible with allogeneic transplantation. Advances in molecular biology, and basic and applied immunology, have led to promising approaches such as genetically engineered T cells with chimeric antigen receptors and T-cell receptors targeting myeloma-specific epitopes, vaccine primed ex vivo expanded autologous T cells, expanded marrow-infiltrating lymphocytes, and plasma cell/dendritic cell fusion vaccines...
December 2, 2016: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/27910822/prolonged-in-vitro-precultivation-alleviates-post-implantation-inflammation-and-promotes-stable-subcutaneous-cartilage-formation-in-a-goat-model
#7
Yi Liu, Dan Li, Zongqi Yin, Xusong Luo, Wei Liu, Wenjie Zhang, Zhiyong Zhang, Yilin Cao, Yu Liu, Guangdong Zhou
Synthetic biodegradable scaffolds such as polylactic acid coated polyglycolic acid (PLA-PGA) are especially suitable for engineering shaped cartilage such as auricle, but they induce a serious inflammatory reaction particularly in the immunologically aggressive subcutaneous site, leading to resorption of the engineered autologous cartilage. Our previous study in a rabbit model has demonstrated 2 weeks of in vitro precultivation could significantly alleviate the post-implantation inflammation induced by PLA-PGA engineered cartilaginous grafts, but reproduction of this result failed in a preclinical goat model...
December 2, 2016: Biomedical Materials
https://www.readbyqxmd.com/read/27907157/human-bone-derived-collagen-for-the-development-of-an-artificial-corneal-endothelial-graft-in-vivo-results-in-a-rabbit-model
#8
Natalia Vázquez, Manuel Chacón, Carlos A Rodríguez-Barrientos, Jesús Merayo-Lloves, Miguel Naveiras, Begoña Baamonde, Jose F Alfonso, Iriana Zambrano-Andazol, Ana C Riestra, Álvaro Meana
Corneal keratoplasty (penetrating or lamellar) using cadaveric human tissue, is nowadays the main treatment for corneal endotelial dysfunctions. However, there is a worldwide shortage of donor corneas available for transplantation and about 53% of the world's population have no access to corneal transplantation. Generating a complete cornea by tissue engineering is still a tough goal, but an endothelial lamellar graft might be an easier task. In this study, we developed a tissue engineered corneal endothelium by culturing human corneal endothelial cells on a human purified type I collagen membrane...
2016: PloS One
https://www.readbyqxmd.com/read/27907088/silver-nanoparticle-directed-mast-cell-degranulation-is-mediated-through-calcium-and-pi3k-signaling-independent-of-the-high-affinity-ige-receptor
#9
Nasser B Alsaleh, Indushekhar Persaud, Jared M Brown
Engineered nanomaterial (ENM)-mediated toxicity often involves triggering immune responses. Mast cells can regulate both innate and adaptive immune responses and are key effectors in allergic diseases and inflammation. Silver nanoparticles (AgNPs) are one of the most prevalent nanomaterials used in consumer products due to their antimicrobial properties. We have previously shown that AgNPs induce mast cell degranulation that was dependent on nanoparticle physicochemical properties. Furthermore, we identified a role for scavenger receptor B1 (SR-B1) in AgNP-mediated mast cell degranulation...
2016: PloS One
https://www.readbyqxmd.com/read/27905838/engineering-hiv-specific-immunity-with-chimeric-antigen-receptors
#10
Scott G Kitchen, Jerome A Zack
HIV remains a highly important public health and clinical issue despite many recent advances in attempting to develop a cure, which has remained elusive for most people infected with HIV. HIV disease can be controlled with pharmacologic therapies; however, these treatments are expensive, may have severe side effects, and are not curative. Consequently, an improved means to control or eliminate HIV replication is needed. Cytotoxic T lymphocytes (CTLs) play a critical role in controlling viral replication and are an important part in the ability of the immune response to eradicate most viral infections...
December 2016: AIDS Patient Care and STDs
https://www.readbyqxmd.com/read/27905089/novel-paradigm-for-immunotherapy-of-ovarian-cancer-by-engaging-prophylactic-immunity-against-hepatitis-b-virus
#11
Marek Malecki, Emily Putzer, Caroline Quach, Chaitanya Dodivenaka, Xenia Tombokan
BACKGROUND: Only eight women out of one hundred diagnosed with ovarian epithelial cancers, which progressed to the clinical stage IV, survive 10 years. First line therapies: surgery, chemotherapy, and radiation therapy inflict very serious iatrogenic consequences. Passive immunotherapy of ovarian cancers offers only low efficacy. Prophylactic and therapeutic vaccines for ovarian cancers are not available. Interestingly, prophylactic vaccines for Hepatitis B Viruses (HBV) are very effective...
December 2016: Clinical and Translational Medicine
https://www.readbyqxmd.com/read/27903221/in-vitro-generated-mesenchymal-stem-cells-suitable-tools-to-target-insulin-dependent-diabetes-mellitus
#12
Shruti D Dave, Patel C N, Patel J V, Thakkar U G
A synergy of a pre-accumulated genes with an autoimmunity advancing to slow abolition of pancreatic beta-cells causes insulin deficiency and results enrooting insulin dependent diabetes mellitus (IDDM). As per WHO data worldwide about 150 million people are diabetic and the number may rise to more than double by the year 2025. Any absolute cure for IDDM is not available yet, and one of the credible advent in the field include cell-based therapy. At this conjecture, mesenchymal stem cells (MSC) seems to have a specific and beneficial characteristics due to their in vivo as well as in vitro potential to mimic a pancreatic endocrine phenotype and immune-regulatory actions...
November 21, 2016: Current Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/27902325/targeting-naturally-occurring-epitope-variants-of-hepatitis-c-virus-with-high-affinity-t-cell-receptors
#13
Huajun Zhang, Jianbing Zhang, Lei Chen, Zhiming Weng, Ye Tian, Haifeng Zhao, Youjia Li, Lin Chen, Zhaoduan Liang, Hongjun Zheng, Wenzhuo Zhao, Shi Zhong, Yi Li
Hepatitis C virus (HCV) readily establishes chronic infection, which is characterized by failure of virus-specific CD8+ T cells. HCV uses epitope mutation and T-cell exhaustion to escape from the host immune response. Previously, we engineered high-affinity T-cell receptors (HATs) targeting HIV escape mutants. In this study, the affinity of a T-cell receptor specific for the human leukocyte antigen (HLA)-A2-restricted HCV immunodominant epitope NS3 1406-1415 (KLVALGINAV) was improved from a KD of 6.6 µM to 40 pM...
November 11, 2016: Journal of General Virology
https://www.readbyqxmd.com/read/27899571/engineering-robust-and-tunable-spatial-structures-with-synthetic-gene-circuits
#14
Wentao Kong, Andrew E Blanchard, Chen Liao, Ting Lu
Controllable spatial patterning is a major goal for the engineering of biological systems. Recently, synthetic gene circuits have become promising tools to achieve the goal; however, they need to possess both functional robustness and tunability in order to facilitate future applications. Here we show that, by harnessing the dual signaling and antibiotic features of nisin, simple synthetic circuits can direct Lactococcus lactis populations to form programmed spatial band-pass structures that do not require fine-tuning and are robust against environmental and cellular context perturbations...
November 28, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27895106/saliva-exosomes-from-pancreatic-tumor-bearing-mice-modulate-nk-cell-phenotype-and-antitumor-cytotoxicity
#15
Stergios Katsiougiannis, David Chia, Yong Kim, Ram P Singh, David T W Wong
Tumor exosomes are emerging as antitumor immunity regulators; however, their effects on secondary exosome secretion by distal organs have not been explored. We have previously demonstrated that suppression of exosomes at the distal tumor site of pancreatic ductal adenocarcinoma (PDAC) ablated the development of salivary biomarker profile. Here, we explore the function of salivary exosomes from tumor-bearing mice in immune surveillance. We provide evidence that salivary exosomes from mice with PDAC exhibit a suppressive effect that results in reduced tumor-killing capacity by NK cells...
November 28, 2016: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/27892871/phenotypic-modulation-of-porcine-cd14-monocytes-natural-killer-natural-killer-t-cells-and-cd8%C3%AE-%C3%AE-t-cell-subsets-by-an-antibody-derived-killer-peptide-kp
#16
Luca Ferrari, Paolo Borghetti, Giulia Ferrarini, Elena De Angelis, Elena Canelli, Giulia Ogno, Alessia Catella, Tecla Ciociola, Walter Magliani, Paolo Martelli
An engineered killer peptide (KP) based on a recombinant anti-idiotypic antibody representing the functional image of a yeast killer toxin (KT) was demonstrated to mediate antimicrobial effects against fungi and viruses. KP binds to murine dendritic cells and macrophages and up-regulate co-receptor expression, thus sustaining CD4+ lymphocyte activation. No immunological data are available in domestic animals thus KP-induced immunomodulation was evaluated in porcine monocyte and lymphocyte subsets. PBMC from healthy adult pigs were stimulated with KP or a scramble peptide (SP), or kept unstimulated for 24, 48 and 72h, and subsequently analyzed by flow cytometry...
September 14, 2016: Research in Veterinary Science
https://www.readbyqxmd.com/read/27891129/immunological-and-translational-aspects-of-nk-cell-based-antitumor-immunotherapies
#17
REVIEW
Maxim Shevtsov, Gabriele Multhoff
Natural killer (NK) cells play a pivotal role in the first line of defense against cancer. NK cells that are deficient in CD3 and a clonal T cell receptor (TCR) can be subdivided into two major subtypes, CD56(dim)CD16(+) cytotoxic and CD56(bright)CD16(-) immunoregulatory NK cells. Cytotoxic NK cells not only directly kill tumor cells without previous stimulation by cytotoxic effector molecules, such as perforin and granzymes or via death receptor interactions, but also act as regulatory cells for the immune system by secreting cytokines and chemokines...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/27889408/an-rna-based-fluorescent-biosensor-for-high-throughput-analysis-of-the-cgas-cgamp-sting-pathway
#18
Debojit Bose, Yichi Su, Assaf Marcus, David H Raulet, Ming C Hammond
In mammalian cells, the second messenger (2'-5',3'-5') cyclic guanosine monophosphate-adenosine monophosphate (2',3'-cGAMP), is produced by the cytosolic DNA sensor cGAMP synthase (cGAS), and subsequently bound by the stimulator of interferon genes (STING) to trigger interferon response. Thus, the cGAS-cGAMP-STING pathway plays a critical role in pathogen detection, as well as pathophysiological conditions including cancer and autoimmune disorders. However, studying and targeting this immune signaling pathway has been challenging due to the absence of tools for high-throughput analysis...
November 18, 2016: Cell Chemical Biology
https://www.readbyqxmd.com/read/27883926/application-of-genetically-engineered-salmonella-typhimurium-for-interferon-gamma-induced-therapy-against-melanoma
#19
Wonsuck Yoon, Yoo Chang Park, Jinseok Kim, Yang Seok Chae, Jung Hye Byeon, Sang-Hyun Min, Sungha Park, Young Yoo, Yong Keun Park, Byeong Mo Kim
Salmonella have been experimentally used as anti-cancer agents, because they show selective growth in tumours. In this study, we genetically modified attenuated Salmonella typhimurium to express and secrete interferon-gamma (IFN-γ) as a tumouricidal agent to enhance the therapeutic efficacy of Salmonella. IFN-γ was fused to the N-terminal region (residues 1-160) of SipB (SipB160) for secretion from bacterial cells. Attenuated S. typhimurium expressing recombinant IFN-γ (S. typhimurium (IFN-γ)) invaded the melanoma cells and induced cytotoxicity...
November 21, 2016: European Journal of Cancer
https://www.readbyqxmd.com/read/27881707/a-cd80-biased-ctla4-ig-fusion-protein-with-superior-in-vivo-efficacy-by-simultaneous-engineering-of-affinity-selectivity-stability-and-fcrn-binding
#20
Julie Douthwaite, Jacques Moisan, Cyril Privezentzev, Blagoje Soskic, Shereen Sabbah, Suzanne Cohen, Andie Collinson, Elizabeth England, Catherine Huntington, Ben Kemp, Li Zhuang, Suzanne Hudak, D Gareth Rees, Debbie Goldberg, Chris Barton, Linda Chang, Inna Vainshtein, Meina Liang, Laurie Iciek, Philip Ambery, Mark Peakman, Tristan J Vaughan, Tim I M Tree, David M Sansom, Michael A Bowen, Ralph R Minter, Lutz Jermutus
Affinity- and stability-engineered variants of CTLA4-Ig fusion molecules with enhanced pharmacokinetic profiles could yield improved therapies with the potential of higher efficacy and greater convenience to patients. In this study, to our knowledge, we have, for the first time, used in vitro evolution to simultaneously optimize CTLA4 affinity and stability. We selected for improved binding to both ligands, CD80 and CD86, and screened as dimeric Fc fusions directly in functional assays to identify variants with stronger suppression of in vitro T cell activation...
November 23, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
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