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https://www.readbyqxmd.com/read/29029499/generation-and-characterization-of-erbb2-car-engineered-cytokine-induced-killer-cells-for-the-treatment-of-high-risk-soft-tissue-sarcoma-in-children
#1
Michael Merker, Verena Pfirrmann, Sarah Oelsner, Simone Fulda, Thomas Klingebiel, Winfried S Wels, Peter Bader, Eva Rettinger
Pediatric patients with recurrent, refractory or advanced soft tissue sarcoma (STS) who are simultaneously showing signs of cumulative treatment toxicity are in need of novel therapies. In this preclinical analysis, we identified ErbB2 as a targetable antigen on STS cells and used cytokine-induced killer (CIK) cells transduced with the lentiviral 2(nd)-generation chimeric antigen receptor (CAR) vector pS-5.28.z-IEW to target ErbB2-positive tumors. Solely CIK cell subsets with the CD3(+) T cell phenotype showed up to 85% cell surface expression of the respective CAR...
September 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/29027233/dysregulated-cellular-functions-and-cell-stress-pathways-provide-critical-cues-for-activating-and-targeting-natural-killer-cells-to-transformed-and-infected-cells
#2
REVIEW
David H Raulet, Assaf Marcus, Laurent Coscoy
Natural killer (NK) cells recognize and kill cancer cells and infected cells by engaging cell surface ligands that are induced preferentially or exclusively on these cells. These ligands are recognized by activating receptors on NK cells, such as NKG2D. In addition to activation by cell surface ligands, the acquisition of optimal effector activity by NK cells is driven in vivo by cytokines and other signals. This review addresses a developing theme in NK cell biology: that NK-activating ligands on cells, and the provision of cytokines and other signals that drive high effector function in NK cells, are driven by abnormalities that arise from transformation or the infected state...
November 2017: Immunological Reviews
https://www.readbyqxmd.com/read/29023581/activating-and-inhibitory-receptors-on-natural-killer-cells-in-patients-with-systemic-lupus-erythematosis-regulation-with-interleukin-15
#3
Syh-Jae Lin, Ming-Ling Kuo, Hsiu-Shan Hsiao, Pei-Tzu Lee, Ji-Yih Chen, Jing-Long Huang
Natural killer (NK) cells may play an important role in the pathogenesis of SLE. Interleukin(IL)-15, an NK-enhancing cytokine, is over-expressed in SLE patients. In the present study, we examined the effect of IL-15 on NK cytotoxicity of SLE patients, and the expression of various activating and inhibitory NK receptors on NK cells from SLE patients in relation to disease activity. We also sought to determine how IL-15 would affect the NK receptor expression on NK cells from SLE patients. PBMCs were collected from 88 SLE patients with inactive disease activity (SLEDAI score<6) and active disease activity (SLEDAI score≥6), 26 age-matched healthy adults were used as controls...
2017: PloS One
https://www.readbyqxmd.com/read/28994628/effects-of-total-flavonoids-of-sea-buckthorn-hippophae-rhamnoides-l-on-cytotoxicity-of-nk92-mi-cells
#4
Diandong Hou, Decheng Wang, Xiande Ma, Wenna Chen, Shengnan Guo, Hongquan Guan
Sea buckthorn ( Hippophae rhamnoides L.) has multifarious medicinal properties including immunoregulatory effect. The total flavonoids of Hippophae rhamnoides L. (TFH) are the main active components isolated from berries of sea buckthorn. The aim of this study was to evaluate the effects of TFH on the cytotoxicity of NK92-MI cells and its possible mechanisms. NK92-MI cells were treated with TFH (2.5 or 5.0 mg/L) or phosphate-buffered saline (PBS) for 24 h, the cytotoxicity against K562 was detected by measuring the release of lactate dehydrogenase (LDH), expression levels of NCRs (NKp30, NKp44, NKp46) and NKG2D were detected by flow cytometry, and expression levels of perforin and granzyme B were detected by western blot...
October 1, 2017: International Journal of Immunopathology and Pharmacology
https://www.readbyqxmd.com/read/28986447/innate-immune-recognition-of-double-stranded-rna-triggers-increased-expression-of-nkg2d-ligands-after-virus-infection
#5
Gloria Esteso, Susana Guerra, Mar Valés-Gómez, Hugh T Reyburn
Self/non-self discrimination by the innate immune system relies on germline-encoded, non-rearranging receptors expressed by innate immune cells recognizing conserved pathogen-associated molecular patterns. The natural killer group 2D (NKG2D) receptor is a potent immune-activating receptor that binds human genome-encoded ligands, whose expression is negligible in normal tissues, but increased in stress and disease conditions for reasons that are incompletely understood. Here it is not clear how the immune system reconciles receptor binding of self-proteins with self/non-self discrimination to avoid autoreactivity...
October 6, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28977824/changes-of-peripheral-lymphocyte-subsets-and-cytokine-environment-during-aging-and-deteriorating-gastrointestinal-tract-health-status
#6
Jing Wang, Guodong Yang, Dongfang Wang, Kuiliang Liu, Yongchao Ma, Hong Liu, Jing Wu, Min Fang
Human immune senescence accompanies with the physical and physiological frailty. The functional change and shift of NK, NKT and T cell subsets by aging have been widely studied. However, it remains largely unclear how the aging and disease conditions affect the distribution of lymphocytes. In the present study, 233 subjects with age range from 20 to 87 year old, including healthy people, people with chronic gastrointestinal tract disease or cancers were investigated. We found that the proportion of NK cells, CD8(+) T cells and NKT cells remained relatively unchanged with aging...
September 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28972539/cd56bright-nk-cells-exhibit-potent-antitumor-responses-following-il-15-priming
#7
Julia A Wagner, Maximillian Rosario, Rizwan Romee, Melissa M Berrien-Elliott, Stephanie E Schneider, Jeffrey W Leong, Ryan P Sullivan, Brea A Jewell, Michelle Becker-Hapak, Timothy Schappe, Sara Abdel-Latif, Aaron R Ireland, Devika Jaishankar, Justin A King, Ravi Vij, Dennis Clement, Jodie Goodridge, Karl-Johan Malmberg, Hing C Wong, Todd A Fehniger
NK cells, lymphocytes of the innate immune system, are important for defense against infectious pathogens and cancer. Classically, the CD56dim NK cell subset is thought to mediate antitumor responses, whereas the CD56bright subset is involved in immunomodulation. Here, we challenge this paradigm by demonstrating that brief priming with IL-15 markedly enhanced the antitumor response of CD56bright NK cells. Priming improved multiple CD56bright cell functions: degranulation, cytotoxicity, and cytokine production...
October 3, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28971893/the-crosstalk-between-esc-and-m%C3%AF-impairs-cytotoxicity-of-nk-cell-by-secreting-il-10-and-tgf-%C3%AE-in-ems
#8
Hui-Li Yang, Wen-Jie Zhou, Kai-Kai Chang, Jie Mei, Li-Qing Huang, Ming-Yan Wang, Yi Meng, Si-Yao Ha, Da-Jin Li, Ming-Qing Li
The dysfunction of NK cells in women with endometriosis (EMS) contributes to the immune escape of menstrual endometrial fragments refluxed into the peritoneal cavity. The reciprocal communications between endometrial stromal cells (ESCs) and lymphocytes facilitate the development of EMS. However, the mechanism of these communications on cytotoxicity of natural killer (NK) cells in endometriotic milieus is still larger unknown. To imitate the local immune microenvironment, the co-culture systems of ESCs from patients with EMS and monocyte-derived macrophages or of ESCs, macrophages and NK cells were constructed...
October 2, 2017: Reproduction: the Official Journal of the Society for the Study of Fertility
https://www.readbyqxmd.com/read/28967637/anti-cancer-efficiency-of-natural-killer-cells-differentiated-from-human-adipose-tissue-derived-mesenchymal-stem-cells-and-transfected-with-mirna150
#9
A Karlitepe, H Kabadayi, S Vatansever, M Gurdal, C Gunduz, G Ercan
AIM: The aim of this study is to investigate the effects of miR150 transfection on NK-like cells differentiated from adipose tissue derived mesenchymal stem cells (AD-MSCs). METHODS: NK-like cells were differentiated from AD-MSCs and activated by miR150 transfection. Transfected/non-transfected NK-like cells were characterized by immunohistochemical and RT-PCR analyzes. Apoptotic efficiency of the transfected/non-transfected NK-like cells on pancreatic cancer cells PANC1 were determined by TUNEL and RT-PCR...
September 2017: Experimental Oncology
https://www.readbyqxmd.com/read/28951779/cd4-t-cells-and-natural-killer-cells-biomarkers-for-hepatic-fibrosis-in-human-immunodeficiency-virus-hepatitis-c-virus-coinfected-patients
#10
Natalia Laufer, Diego Ojeda, María Laura Polo, Ana Martinez, Héctor Pérez, Gabriela Turk, Pedro Cahn, Norberto Walter Zwirner, Jorge Quarleri
AIM: To characterize peripheral blood natural killer (NK) cells phenotypes by flow cytometry as potential biomarker of liver fibrosis in human immunodeficiency virus (HIV)/hepatitis C virus (HCV) coinfected patients. METHODS: Peripheral mononuclear cells from 24 HIV/HCV (HBV negative) coinfected and 5 HIV/HCV/HBV seronegative individuals were evaluated. HIV/HCV coinfected patients were divided in to groups: G1, patients with METAVIR F0-F2 and G2, patients with METAVIR F3-F4...
September 8, 2017: World Journal of Hepatology
https://www.readbyqxmd.com/read/28947538/phenotypic-and-functional-characterization-of-circulatory-splenic-and-hepatic-nk-cells-in-simian-immunodeficiency-virus-controlling-macaques
#11
Diego A Vargas-Inchaustegui, Sabrina Helmold Hait, Hye Kyung Chung, Jigna Narola, Tanya Hoang, Marjorie Robert-Guroff
NK cells are key components of the immune system because of their rapid response potential and their ability to mediate cytotoxic and immunomodulatory functions. Additionally, NK cells have recently been shown to persist for long periods in vivo and to have the capacity to establish immunologic memory. In the current study, we assessed the phenotype and function of circulatory and tissue-resident NK cells in a unique cohort of SIV-controlling rhesus macaques that maintained low to undetectable levels of viremia in the chronic phase of infection...
September 25, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28944101/soluble-micb-in-plasma-and-urine-explains-population-expansions-of-nkg2d-cd4-t-cells-inpatients-with-juvenile-onset-systemic-lupus-erythematosus
#12
Satoru Hamada, Andrea Caballero-Benitez, Kate L Duran, Anne M Stevens, Thomas Spies, Veronika Groh
Abnormal NKG2D ligand expression has been implicated in the initiation and maintenance of various auto-inflammatory disorders including systemic lupus erythematosus (SLE). This study's goal was to identify the cellular contexts providing NKG2D ligands for stimulation of the immunosuppressive NKG2D(+)CD4 T cell subset that has been implicated in modulating juvenile-onset SLE disease activity. Although previous observations with NKG2D(+)CD4 T cells in healthy individuals pointed towards peripheral B cell and myeloid cell compartments as possible sites of enhanced NKG2DL presence, we found no evidence for a disease-associated increase of NKG2DL-positivity among juvenile-onset SLE B cells and monocytes...
March 2017: Open Journal of Immunology
https://www.readbyqxmd.com/read/28943878/triplebody-mediates-increased-anti-leukemic-reactivity-of-il-2-activated-donor-natural-killer-nk-cells-and-impairs-viability-of-their-cd33-expressing-nk-subset
#13
Stephan Kloess, Alessa Ede Valverde da Silva, Olaf Oberschmidt, Tanja Gardlowski, Nadine Matthies, Maulik Vyas, Lubomir Arseniev, Michael Heuser, Elke Pogge von Strandmann, Ulrike Köhl
Natural killer cells (NK) are essential for the elimination of resistant acute myeloid and acute lymphoblastic leukemia (AML and ALL) cells. NK cell-based immunotherapies have already successfully entered for clinical trials, but limitations due to immune escape mechanisms were identified. Therefore, we extended our established NK cell protocol by integration of the previously investigated powerful trispecific immunoligand ULBP2-aCD19-aCD33 [the so-called triplebodies (TBs)] to improve the anti-leukemic specificity of activated NK cells...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28932644/romidepsin-alone-or-in-combination-with-anti-cd20-chimeric-antigen-receptor-expanded-natural-killer-cells-targeting-burkitt-lymphoma-in-vitro-and-in-immunodeficient-mice
#14
Yaya Chu, Ashlin Yahr, Brian Huang, Janet Ayello, Matthew Barth, Mitchell S Cairo
Facilitating the development of alternative targeted therapeutic strategies is urgently required to improve outcome or circumvent chemotherapy resistance in children, adolescents, and adults with recurrent/refractory de novo mature B-cell (CD20) non-Hodgkin lymphoma, including Burkitt lymphoma (BL). Romidepsin, a histone deacetylase inhibitor (HDACi), has been used to treat cutaneous T-cell lymphoma. We have demonstrated the significant anti-tumor effect of anti-CD20 chimeric antigen receptor (CAR) modified expanded peripheral blood natural killer (exPBNK) against rituximab-sensitive and -resistant BL...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28932639/soluble-nkg2d-ligands-in-the-ovarian-cancer-microenvironment-are-associated-with-an-adverse-clinical-outcome-and-decreased-memory-effector-t-cells-independent-of-nkg2d-downregulation
#15
Maulik Vyas, Silke Reinartz, Nathalie Hoffmann, Katrin S Reiners, Sonja Lieber, Julia M Jansen, Uwe Wagner, Rolf Müller, Elke Pogge von Strandmann
The immune receptor NKG2D is predominantly expressed on NK cells and T cell subsets and confers anti-tumor activity. According to the current paradigm, immune surveillance is counteracted by soluble ligands shed into the microenvironment, which down-regulate NKG2D receptor expression. Here, we analyzed the clinical significance of the soluble NKG2D ligands sMICA and sULBP2 in the malignancy-associated ascites of ovarian cancer. We show that high levels of sMICA and sULBP2 in ascites were associated with a poor prognosis...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28932638/the-anti-slamf7-antibody-elotuzumab-mediates-nk-cell-activation-through-both-cd16-dependent-and-independent-mechanisms
#16
Tatiana Pazina, Ashley M James, Alexander W MacFarlane, Natalie A Bezman, Karla A Henning, Christine Bee, Robert F Graziano, Michael D Robbins, Adam D Cohen, Kerry S Campbell
Elotuzumab is a humanized therapeutic monoclonal antibody directed to the surface glycoprotein SLAMF7 (CS1, CRACC, CD319), which is highly expressed on multiple myeloma (MM) tumor cells. Improved clinical outcomes have been observed following treatment of MM patients with elotuzumab in combination with lenalidomide or bortezomib. Previous work showed that elotuzumab stimulates NK cell-mediated antibody-dependent cellular cytotoxicity (ADCC), via Fc-domain engagement with FcγRIIIa (CD16). SLAMF7 is also expressed on NK cells, where it can transmit stimulatory signals...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28926962/anti-nkg2d-mab-a-new-treatment-for-crohn-s-disease
#17
REVIEW
Kasper Vadstrup, Flemming Bendtsen
Crohn's disease (CD) and ulcerative colitis (UC) are immunologically-mediated, debilitating conditions resulting from destructive inflammation of the gastrointestinal tract. The pathogenesis of IBD is incompletely understood, but is considered to be the result of an abnormal immune response with a wide range of cell types and proteins involved. Natural Killer Group 2D (NKG2D) is an activating receptor constitutively expressed on human Natural Killer (NK), γδ T, mucosal-associated invariant T (MAIT), CD56⁺ T, and CD8⁺ T cells...
September 16, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28915646/interleukin-15-stimulates-natural-killer-cell-mediated-killing-of-both-human-pancreatic-cancer-and-stellate-cells
#18
Jonas R M Van Audenaerde, Jorrit De Waele, Elly Marcq, Jinthe Van Loenhout, Eva Lion, Johan M J Van den Bergh, Ralf Jesenofsky, Atsushi Masamune, Geert Roeyen, Patrick Pauwels, Filip Lardon, Marc Peeters, Evelien L J Smits
Pancreatic ductal adenocarcinoma (PDAC) is the 4(th) leading cause of cancer-related death in Western countries with a 5-year survival rate below 5%. One of the hallmarks of this cancer is the strong desmoplastic reaction within the tumor microenvironment (TME), orchestrated by activated pancreatic stellate cells (PSC). This results in a functional and mechanical shield which causes resistance to conventional therapies. Aiming to overcome this resistance by tackling the stromal shield, we assessed for the first time the capacity of IL-15 stimulated natural killer (NK) cells to kill PSC and pancreatic cancer cells (PCC)...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28912779/v%C3%AE-4-%C3%AE-%C3%AE-t-cells-aggravate-severe-h1n1-influenza-virus-infection-induced-acute-pulmonary-immunopathological-injury-via-secreting-interleukin-17a
#19
Chunxue Xue, Mingjie Wen, Linlin Bao, Hui Li, Fengdi Li, Meng Liu, Qi Lv, Yunqing An, Xulong Zhang, Bin Cao
The influenza A (H1N1) pdm09 virus remains a critical global health concern and causes high levels of morbidity and mortality. Severe acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are the major outcomes among severely infected patients. Our previous study found that interleukin (IL)-17A production by humans or mice infected with influenza A (H1N1) pdm09 substantially contributes to ALI and subsequent morbidity and mortality. However, the cell types responsible for IL-17A production during the early stage of severe influenza A (H1N1) pdm09 infection remained unknown...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28894091/expansion-of-cytotoxic-natural-killer-cells-using-irradiated-autologous-peripheral-blood-mononuclear-cells-and-anti-cd16-antibody
#20
Hong-Rae Lee, Cheol-Hun Son, Eun-Kyoung Koh, Jae-Ho Bae, Chi-Dug Kang, Kwangmo Yang, You-Soo Park
Natural killer (NK) cells are considered a promising strategy for cancer treatment. Various methods for large-scale NK cell expansion have been developed, but they should guarantee that no viable cells are mixed with the expanded NK cells because most methods involve cancer cells or genetically modified cells as feeder cells. We used an anti-CD16 monoclonal antibody (mAb) and irradiated autologous peripheral blood mononuclear cells (PBMCs) (IrAPs) to provide a suitable environment (activating receptor-ligand interactions) for the NK cell expansion...
September 11, 2017: Scientific Reports
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