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https://www.readbyqxmd.com/read/28651074/chimeric-antigen-receptor-engineered-natural-killer-and-natural-killer-t-cells-for-cancer-immunotherapy
#1
REVIEW
Dominique Bollino, Tonya J Webb
Natural killer (NK) cells of the innate immune system and NK T (NKT) cells, which have roles in both the innate and adaptive responses, are unique lymphocyte subsets that have similarities in their functions and phenotypes. Both cell types can rapidly respond to the presence of tumor cells and participate in immune surveillance and antitumor immune responses. This has incited interest in the development of novel cancer therapeutics based on NK and NKT cell manipulation. Chimeric antigen receptors (CARs), generated through the fusion of an antigen-binding region of a monoclonal antibody or other ligand to intracellular signaling domains, can enhance lymphocyte targeting and activation toward diverse malignancies...
June 9, 2017: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/28647908/cmv-immune-evasion-and-manipulation-of-the-immune-system-with-aging
#2
REVIEW
Sarah E Jackson, Anke Redeker, Ramon Arens, Debbie van Baarle, Sara P H van den Berg, Chris A Benedict, Luka Čičin-Šain, Ann B Hill, Mark R Wills
Human cytomegalovirus (HCMV) encodes numerous proteins and microRNAs that function to evade the immune response and allow the virus to replicate and disseminate in the face of a competent innate and acquired immune system. The establishment of a latent infection by CMV, which if completely quiescent at the level of viral gene expression would represent an ultimate in immune evasion strategies, is not sufficient for lifelong persistence and dissemination of the virus. CMV needs to reactivate and replicate in a lytic cycle of infection in order to disseminate further, which occurs in the face of a fully primed secondary immune response...
June 24, 2017: GeroScience
https://www.readbyqxmd.com/read/28641074/development-of-novel-antigen-receptors-for-car-t-cell-therapy-directed-toward-solid-malignancies
#3
REVIEW
David Chen, James Yang
Development of chimeric antigen receptor (CAR) T cells have led to remarkable successes in the treatment of B-cell malignancies with anti-CD19 CAR. Here we discuss the development of novel antigen receptors for use in solid malignancies with respect to target antigens, receptor design, and T cell manipulations.
June 1, 2017: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/28638729/cellular-immunotherapies-for-cancer
#4
REVIEW
Pedro Berraondo, Sara Labiano, Luna Minute, Iñaki Etxeberria, Marcos Vasquez, Alvaro Sanchez-Arraez, Alvaro Teijeira, Ignacio Melero
Lessons learned over decades on the use of gene and cell therapies have found clinical applicability in the field of cancer immunotherapy. On December 16(th), 2016 a symposium was held in Pamplona (Spain) to analyze and discuss the critical points for the clinical success of adoptive cell transfer strategies in cancer immunotherapy. Cellular immunotherapy is being currently exploited for the development of new cancer vaccines using ex vivo manipulated dendritic cells or to enhance the number of effector cells, transferring reinvigorated NK cells or T cells...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28637877/ex-vivoexpanded-adaptive-nk-cells-effectively-kill-primary-acute-lymphoblastic-leukemia-cells
#5
Lisa L Liu, Vivien Beziat, Vincent Oei Yi Sheng, Aline Pfefferle, Marie Schaffer, Soren Lehmann, Eva Hellstrom-Lindberg, Stefan Soderhall, Mats Heyman, Dan Grander, Karl-Johan Malmberg
Manipulation of human NK cell repertoires promises more effective strategies for NK cell-based cancer immunotherapy. A subset of highly differentiated NK cells, termed adaptive NK cells, expands naturally in vivo in response to human cytomegalovirus (HCMV) infection, carries unique repertoires of inhibitory killer cell immunoglobulin-like receptors (KIRs), and displays strong cytotoxicity against tumor cells. Here, we established a robust and scalable protocol for ex vivo generation and expansion of adaptive NK cells for cell therapy against pediatric acute lymphoblastic leukemia (ALL)...
June 21, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28637663/ny-eso-1-tcr-single-edited-central-memory-and-memory-stem-t-cells-to-treat-multiple-myeloma-without-inducing-gvhd
#6
Sara Mastaglio, Pietro Genovese, Zulma Magnani, Eliana Ruggiero, Elisa Landoni, Barbara Camisa, Giulia Schiroli, Elena Provasi, Angelo Lombardo, Andreas Reik, Nicoletta Cieri, Martina Rocchi, Giacomo Oliveira, Giulia Escobar, Monica Casucci, Bernhard Gentner, Antonello Spinelli, Anna Mondino, Attilio Bondanza, Luca Vago, Maurilio Ponzoni, Fabio Ciceri, Michael C Holmes, Luigi Naldini, Chiara Bonini
Transfer of T cell receptors (TCR) specific for tumor-associated antigens is a promising approach for cancer immunotherapy. We developed the TCR gene editing technology, that is based on the knockout of the endogenous TCR α and β genes, followed by the introduction of tumor-specific TCR genes, and that proved safer and more effective than conventional TCR gene transfer. While successful, complete editing requires extensive cell manipulation and four transduction procedures. Here we propose a novel and clinically feasible 'single TCR editing' (SE) approach, based on the disruption of the endogenous TCR α chain only, followed by the transfer of genes encoding for a tumor specific TCR...
June 21, 2017: Blood
https://www.readbyqxmd.com/read/28636890/memory-t-cells-a-helpful-guard-for-allogeneic-hematopoietic-stem-cell-transplantation-without-causing-graft-versus-host-disease
#7
REVIEW
Wei Huang, Nelson J Chao
Graft-versus-host disease (GVHD) is a major complication of allogeneic hematopoietic stem cell transplantation (AHSCT) and the major cause of nonrelapse morbidity and mortality of AHSCT. In AHSCT, donor T cells facilitate hematopoietic stem cell (HSC) engraftment, contribute to anti-infection immunity, and mediate graft-versus-leukemia (GVL) responses. However, activated alloreactive T cells also attack recipient cells in vital organs, leading to GVHD. Different T-cell subsets, including naïve T (TN) cells, memory T (TM) cells, and regulatory T (Treg) cells mediate different forms of GVHD and GVL; TN cells mediate severe GVHD, whereas TM cells do not cause GVHD, but preserve T-cell function including GVL...
June 13, 2017: Hematology/oncology and Stem Cell Therapy
https://www.readbyqxmd.com/read/28635677/t-cell-manipulation-strategies-to-prevent-graft-versus-host-disease-in-haploidentical-stem-cell-transplantation
#8
REVIEW
Jayakumar Vadakekolathu, Sergio Rutella
Allogeneic haematopoietic stem cell transplantation (HSCT) from an human leukocyte antigen (HLA)-identical donor can be curative for eligible patients with non-malignant and malignant haematological disorders. HSCT from alternative donor sources, such as HLA-mismatched haploidentical donors, is increasingly considered as a viable therapeutic option for patients lacking HLA-matched donors. Initial attempts at haploidentical HSCT were associated with vigorous bidirectional alloreactivity, leading to unacceptably high rates of graft rejection and graft-versus-host disease (GVHD)...
June 21, 2017: Biomedicines
https://www.readbyqxmd.com/read/28628650/the-human-cytomegalovirus-glycoprotein-pul11-acts-via-cd45-to-induce-t-cell-il-10-secretion
#9
Jasmin Zischke, Panagiota Mamareli, Claudia Pokoyski, Ildar Gabaev, Sabine Buyny, Roland Jacobs, Christine S Falk, Matthias Lochner, Tim Sparwasser, Thomas F Schulz, Penelope C Kay-Fedorov
Human Cytomegalovirus (HCMV) is a widespread pathogen, infection with which can cause severe disease for immunocompromised individuals. The complex changes wrought on the host's immune system during both productive and latent HCMV infection are well known. Infected cells are masked and manipulated and uninfected immune cells are also affected; peripheral blood mononuclear cell (PBMC) proliferation is reduced and cytokine profiles altered. Levels increase of the anti-inflammatory cytokine IL-10, which may be important for the establishment of HCMV infections and is required for the development of high viral titres by murine cytomegalovirus...
June 19, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28617866/characterization-of-trace-metal-content-in-the-developing-zebrafish-embryo
#10
Rebecca T Thomason, Michael A Pettiglio, Carolina Herrera, Clara Kao, Jonathan D Gitlin, Thomas B Bartnikas
Trace metals are essential for health but toxic when present in excess. The maintenance of trace metals at physiologic levels reflects both import and export by cells and absorption and excretion by organs. The mechanism by which this maintenance is achieved in vertebrate organisms is incompletely understood. To explore this, we chose zebrafish as our model organism, as they are amenable to both pharmacologic and genetic manipulation and comprise an ideal system for genetic screens and toxicological studies...
2017: PloS One
https://www.readbyqxmd.com/read/28615415/cutting-edge-the-aging-immune-system-reveals-the-biological-impact-of-direct-antigen-presentation-on-cd8-t-cell-responses
#11
Jennifer L Uhrlaub, Megan J Smithey, Janko Nikolich-Žugich
The vertebrate immune system uses multiple, sometimes redundant, mechanisms to contain pathogenic microorganisms that are always evolving to evade host defenses. Thus, the cowpox virus (CPXV) uses genes encoding CPXV12 and CPXV203 to prevent direct MHC class I presentation of viral peptides by infected cells. However, CD8 T cells are effectively primed against CPXV by cross-presentation of viral Ags in young mice. Old mice accumulate defects in both CD8 T cell activation and cross-presentation. Using a double-deletion mutant (∆12∆203) of CPXV, we show that direct priming of CD8 T cells in old mice yields superior recall responses, establishing a key contribution of this mechanism to host antipoxvirus responses and enhancing our fundamental understanding of how viral manipulation of direct presentation impacts pathogenesis...
June 14, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28615322/in-vivo-manipulation-of-the-extracellular-matrix-induces-vascular-regression-in-a-basal-chordate
#12
Delany Rodriguez, Brian P Braden, Scott W Boyer, Daryl A Taketa, Leah Setar, Chris Calhoun, Alessandro Di Maio, Adam Langenbacher, Megan T Valentine, Anthony W De Tomaso
We investigated the physical role of the extracellular matrix in vascular homeostasis in the basal chordate Botryllus schlosseri, which has a large, transparent extracorporeal vascular network encompassing areas >100 cm(2) We found that the collagen crosslinking enzyme lysyl oxidase is expressed in all vascular cells, and that in vivo inhibition using ß-aminopropionitrile (BAPN) caused a rapid, global regression of the entire network, with some vessels regressing >10 mm within 16 hours. BAPN treatment changed the ultrastructure of collagen fibers in the vessel basement membrane, and the kinetics of regression were dose-dependent...
June 14, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28609587/chemogenetic-modulation-of-g-protein-coupled-receptor-signalling-in-visual-attention-research
#13
Søren H Jørgensen, Ciarán Martin Fitzpatrick, Ulrik Gether, David D P Woldbye, Andreas T Sørensen
Attention is a fundamental cognitive process involved in nearly all aspects of life. Abnormal attention control is a symptom of many neurological disorders, most notably recognized in ADHD (attention deficit hyperactivity disorder). Although attentional performance and its malfunction has been a major area of investigation, it has proven difficult to accurately associate specific neuronal projections, cell types, neurotransmitter systems and receptors with distinct phenotypes owing to its complexity. In this MiniReview, we present a recently invented technology known as Designer Receptors Exclusively Activated by Designer Drugs (DREADDs)...
June 13, 2017: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/28607133/loss-of-thymic-innate-lymphoid-cells-leads-to-impaired-thymopoiesis-in-experimental-graft-vs-host-disease
#14
Jarrod A Dudakov, Anna M Mertelsmann, Margaret H O'Connor, Robert R Jenq, Enrico Velardi, Lauren F Young, Odette M Smith, Richard L Boyd, Marcel R M van den Brink, Alan M Hanash
Graft vs. host disease (GVHD) and post-transplant immunodeficiency are frequently related complications of allogeneic hematopoietic transplantation. Alloreactive donor T cells can damage thymic epithelium, thus limiting new T cell development. While the thymus has a remarkable capacity to regenerate after injury, endogenous thymic regeneration is impaired in GVHD. The mechanisms leading to this regenerative failure are largely unknown. Here we demonstrate in experimental mouse models that GVHD results in depletion of intrathymic group 3 innate lymphoid cells (ILC3s) necessary for thymic regeneration...
June 12, 2017: Blood
https://www.readbyqxmd.com/read/28605808/rat-limbal-niche-cells-prevent-epithelial-stem-progenitor-cells-from-differentiation-and-proliferation-by-inhibiting-notch-signaling-pathway-in-vitro
#15
Jing Li, Szu-Yu Chen, Xin-Yue Zhao, Ming-Chang Zhang, Hua-Tao Xie
Purpose: Limbal niche cells (LNCs) play a pivotal role in regulating limbal epithelial stem/progenitor cells (LESCs). This study aimed to investigate whether Notch signaling is involved in LNCs' regulation of LESCs. Methods: Rat limbus was digested by dispase and collagenase, respectively. Limbal niche cells were isolated by serial passage of collagenase-digested cells on coated Matrigel in a modified embryonic stem cell medium (MESCM). Dispase-isolated cells, with or without LNCs, were seeded on three-dimensional (3D) Matrigel...
June 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/28601924/tgf-%C3%AE-1-silenced-leukemia-cell-derived-exosomes-target-dendritic-cells-to-induce-potent-anti-leukemic-immunity-in-a-mouse-model
#16
Fang Huang, Jiangbo Wan, Siguo Hao, Xiaohui Deng, Linjun Chen, Liyuan Ma
Tumor-derived exosomes (TEX) can induce a specific antitumor immune response and have been developed as a promising tumor vaccine. Despite promising preclinical data, TEX exhibit relatively low efficacy and limited clinical benefit in clinical trials. In the present study, we investigated whether exosomes from the TGF-β1 silenced L1210 cells (LEXTGF-β1si) can enhance the efficacy of DC-based vaccines. We silenced TGF-β1 in L1210 cells with a lentiviral shRNA vector and prepared the LEXTGF-β1si. It was shown that LEXTGF-β1si can significantly decrease TGF-β1 expression of dendritic cells (DC) and effectively promote their maturation and immune function...
June 10, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28600817/il17a-dependent-asymmetric-stem-cell-divisions-are-increased-in-human-psoriasis-a-mechanism-underlying-benign-hyperproliferation
#17
Alexandra Charruyer, Stephen Fong, Giselle Vitcov, Samuel Sklar, Leah Tabernik, Monica Taneja, Melinda Caputo, Catherine Soeung, Lili Yue, Yoshi Uchida, Sarah T Arron, Karen Horton, Robert Foster, Shigetoshi Sano, Jeffrey North, Ruby Ghadially
The balance between asymmetric and symmetric stem cell (SC) divisions is key to tissue homeostasis and dysregulation of this balance has been shown in cancers. We hypothesized that the balance between asymmetric SC divisions (ACDs) and symmetric cell divisions (SCDs) would be dysregulated in the benign hyperproliferation of psoriasis. We found that, whereas SCDs were increased in squamous cell carcinoma (SCC) (human and murine), ACDs were increased in the benign hyperproliferation of psoriasis (human and murine)...
June 10, 2017: Stem Cells
https://www.readbyqxmd.com/read/28598525/retraction-an-400%C3%A2-kda-membrane-associated-complex-that-contains-one-molecule-of-the-resistance-protein-cf-4-by-susana-rivas-tatiana-mucyn-harrold-a-van-den-burg-jacques-vervoort-and-jonathan-d-g-jones
#18
(no author information available yet)
The above article, published online on 26 March 2002 in Wiley Online Library (wileyonlinelibrary.com), and in Volume 29, pp. 783-796 has been retracted by agreement between the authors, the journal Editor-in-Chief, Christoph Benning, and John Wiley & Sons Ltd. The authors have requested that it be retracted because it contains a substantial number of inappropriate image manipulations. These manipulations consist of the reuse or duplication of images, both within the above article and with another manuscript published previously in The Plant Cell (Rivas et al...
June 2017: Plant Journal: for Cell and Molecular Biology
https://www.readbyqxmd.com/read/28596772/epigenetic-regulation-of-matrix-metalloproteinase-1-and-3-expression-in-mycobacterium-tuberculosis-infection
#19
Rachel C Moores, Sara Brilha, Frans Schutgens, Paul T Elkington, Jon S Friedland
In pulmonary tuberculosis (TB), the inflammatory immune response against Mycobacterium tuberculosis (Mtb) is associated with tissue destruction and cavitation, which drives disease transmission, chronic lung disease, and mortality. Matrix metalloproteinase (MMP)-1 is a host enzyme critical for the development of cavitation. MMP expression has been shown to be epigenetically regulated in other inflammatory diseases, but the importance of such mechanisms in Mtb-associated induction of MMP-1 is unknown. We investigated the role of changes in histone acetylation in Mtb-induced MMP expression using inhibitors of histone deacetylases (HDACs) and histone acetyltransferases (HAT), HDAC siRNA, promoter-reporter constructs, and chromatin immunoprecipitation assays...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28589358/somatic-hypermutation-and-affinity-maturation-analysis-using-the-4-hydroxy-3-nitrophenyl-acetyl-np-system
#20
Nicole Heise, Ulf Klein
Somatic hypermutation of immunoglobulin variable region (IgV) genes and affinity maturation of the antibody response are the hallmarks of the germinal center (GC) reaction in T cell-dependent immune responses. Determining the consequences of the experimental manipulation of the GC response on somatic hypermutation and affinity maturation requires the availability of a system that allows measuring these parameters. Immunization of mice of the C57/Bl6 genetic background with the hapten 4-hydroxy-3-nitrophenyl-acetyl (NP) coupled to a carrier protein leads to the predominant usage of one particular IgV heavy chain gene segment, V186...
2017: Methods in Molecular Biology
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