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nkg2d AND tumor target therapy

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https://www.readbyqxmd.com/read/29784005/cd8-t-cells-mediate-the-antitumor-activity-of-frankincense-and-myrrh-in-hepatocellular-carcinoma
#1
Chun Xu, Xian Lu, Wei Liu, Anxian Chen, Gang Meng, Hailin Zhang, Binghua Li, Yonghui Zhang, Junhua Wu, Jiwu Wei
BACKGROUND: Tumor-promoting inflammation is an emerging hallmark of cancer, which participates in both cancer progression and immune escape. Hepatocellular carcinoma (HCC) is a typical inflammation-related cancer with an extremely poor prognosis. Frankincense and myrrh are anti-inflammation agents commonly used in clinic. The purpose of this study is to investigate whether extract of frankincense and myrrh (FM) downregulates inflammatory microenvironment of HCC and thereby restores antitumor immune responses...
May 21, 2018: Journal of Translational Medicine
https://www.readbyqxmd.com/read/29725332/improving-the-efficiency-of-v%C3%AE-9v%C3%AE-2-t-cell-immunotherapy-in-cancer
#2
REVIEW
Timm Hoeres, Manfred Smetak, Dominik Pretscher, Martin Wilhelm
Increasing immunological knowledge and advances in techniques lay the ground for more efficient and broader application of immunotherapies. gamma delta (γδ) T-cells possess multiple favorable anti-tumor characteristics, making them promising candidates to be used in cellular and combination therapies of cancer. They recognize malignant cells, infiltrate tumors, and depict strong cytotoxic and pro-inflammatory activity. Here, we focus on human Vγ9Vδ2 T-cells, the most abundant γδ T-cell subpopulation in the blood, which are able to inhibit cancer progression in various models in vitro and in vivo ...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29528990/nkg2d-immunoligand-rg7s-mica-enhances-nk-cell-mediated-immunosurveillance-in-colorectal-carcinoma
#3
Tong Wang, Fumou Sun, Yang Wang, Jiahao Jiang, Mingzhu Pan, Minne Yuan, Hang Zhang, Xiaodian Du, Kamal Hezam, Kai Song, Min Wang, Juan Zhang
Colorectal carcinoma (CRC) is one of the most common malignant cancers worldwide. The poor response of CRC to chemotherapy has whipped up the interest in targeted therapy with monoclonal antibodies for its potential efficiency. However, cetuximab, as one of the first-line targeted drugs in the treatment of CRC, has drug resistance and poor prognosis in clinic. To address this, a novel bispecific protein with CRC targeting and natural killer (NK) cell triggering was used for treatment. NK cell-mediated immunosurveillance is normally activated by the activating receptor natural killer cell receptor NK group 2, member D (NKG2D), which binds its key ligand major histocompatibility complex (MHC) class I-related chain A (MICA) expressed on the tumor cells...
April 2018: Journal of Immunotherapy
https://www.readbyqxmd.com/read/29391351/t-cell-homing-therapy-for-reducing-regulatory-t-cells-and-preserving-effector-t-cell-function-in-large-solid-tumors
#4
Jiemiao Hu, Chuang Sun, Chantale Bernatchez, Xueqing Xia, Patrick Hwu, Gianpietro Dotti, Shulin Li
PURPOSE: Infused autologous tumor-infiltrating lymphocytes (TILs) and tumor-targeted chimeric antigen receptor (CAR)-T cells typically surround malignant lesions or penetrate small tumor nodules, but fail to penetrate large solid tumors, significantly compromising their antitumor impact. Strategies to overcome this primary challenge are largely required. EXPERIMENTAL DESIGN: We tested the effects of IL-12 plus doxorubicin on T cell penetration and efficacy in solid tumors in a murine lung cancer model, a murine breast carcinoma lung metastasis model and two human xenograft tumor models bearing large tumors (>10 mm)...
February 1, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29342200/inhibiting-tgf-beta-signaling-preserves-the-function-of-highly-activated-in-vitro-expanded-natural-killer-cells-in-aml-and-colon-cancer-models
#5
Folashade Otegbeye, Evelyn Ojo, Stephen Moreton, Nathan Mackowski, Dean A Lee, Marcos de Lima, David N Wald
Natural killer cells harnessed from healthy individuals can be expanded ex vivo using various platforms to produce large doses for adoptive transfer into cancer patients. During such expansion, NK cells are increasingly activated and more efficient at killing cancer cells. Adoptive transfer however introduces these activated cells into a highly immunosuppressive tumor microenvironment mediated in part by excessive transforming growth factor beta (TGF-beta) from both cancer cells and their surrounding stroma...
2018: PloS One
https://www.readbyqxmd.com/read/29222400/nkg2d-based-car-t-cells-and-radiotherapy-exert-synergistic-efficacy-in-glioblastoma
#6
Tobias Weiss, Michael Weller, Matthias Guckenberger, Charles L Sentman, Patrick Roth
Chimeric antigen receptor (CAR) T-cell therapy is an emerging immunotherapy against several malignancies including glioblastoma, the most common and most aggressive malignant primary brain tumor in adults. The challenges in solid tumor immunotherapy comprise heterogenously expressed tumor target antigens and restricted trafficking of CAR T cells to and impaired long-term persistence at the tumor site, as well as the unaddressed integration of CAR T-cell therapy into conventional anticancer treatments. We addressed these questions using a NKG2D-based chimeric antigen receptor construct (chNKG2D) in fully immunocompetent orthotopic glioblastoma mouse models...
February 15, 2018: Cancer Research
https://www.readbyqxmd.com/read/29147621/in-depth-immunophenotyping-of-patients-with-glioblastoma-multiforme-impact-of-steroid-treatment
#7
Guranda Chitadze, Charlotte Flüh, Elgar Susanne Quabius, Sandra Freitag-Wolf, Christian Peters, Marcus Lettau, Jaydeep Bhat, Daniela Wesch, Hans-Heinrich Oberg, Stefanie Luecke, Ottmar Janssen, Michael Synowitz, Janka Held-Feindt, Dieter Kabelitz
Despite aggressive treatment regimens based on surgery and radiochemotherapy, the prognosis of patients with grade IV glioblastoma multiforme (GBM) remains extremely poor, calling for alternative options such as immunotherapy. Immunological mechanisms including the Natural Killer Group 2 member D (NKG2D) receptor-ligand system play an important role in tumor immune surveillance and targeting the NKG2D system might be beneficial. However, before considering any kind of immunotherapy, a precise characterization of the immune system is important, particularly in GBM patients where conventional therapies with impact on the immune system are frequently co-administered...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/29138222/decitabine-enhances-targeting-of-aml-cells-by-cd34-progenitor-derived-nk-cells-in-nod-scid-il2rg-null-mice
#8
Jeannette Cany, Mieke W H Roeven, Janneke S Hoogstad-van Evert, Willemijn Hobo, Frans Maas, Rosalia Franco Fernandez, Nicole M A Blijlevens, Walter J van der Velden, Gerwin Huls, Joop H Jansen, Nicolaas P M Schaap, Harry Dolstra
Combining natural killer (NK) cell adoptive transfer with hypomethylating agents (HMAs) is an attractive therapeutic approach for patients with acute myeloid leukemia (AML). However, data regarding the impact of HMAs on NK cell functionality are mostly derived from in vitro studies with high nonclinical relevant drug concentrations. In the present study, we report a comparative study of azacitidine (AZA) and decitabine (DAC) in combination with allogeneic NK cells generated from CD34+ hematopoietic stem and progenitor cells (HSPC-NK cells) in in vitro and in vivo AML models...
January 11, 2018: Blood
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
#9
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 2nd -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/28915646/interleukin-15-stimulates-natural-killer-cell-mediated-killing-of-both-human-pancreatic-cancer-and-stellate-cells
#10
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/28880014/chimeric-antigen-receptor-car-transduced-natural-killer-cells-in-tumor-immunotherapy
#11
REVIEW
Yuan Hu, Zhi-Gang Tian, Cai Zhang
Natural killer (NK) cells are potential effector cells in cell-based cancer immunotherapy, particularly in the control of hematological malignancies. The chimeric antigen receptor (CAR) is an artificially modified fusion protein that consists of an extracellular antigen recognition domain fused to an intracellular signaling domain. T cells genetically modified with a CAR have demonstrated remarkable success in the treatment of hematological cancers. Compared to T cells, CAR-transduced NK cells (CAR-NK) exhibit several advantages, such as safety in clinical use, the mechanisms by which they recognize cancer cells, and their abundance in clinical samples...
February 2018: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/28771222/microrna-519a-3p-mediates-apoptosis-resistance-in-breast-cancer-cells-and-their-escape-from-recognition-by-natural-killer-cells
#12
Christian Breunig, Jens Pahl, Moritz Küblbeck, Matthias Miller, Daniela Antonelli, Nese Erdem, Cornelia Wirth, Rainer Will, Alexander Bott, Adelheid Cerwenka, Stefan Wiemann
Aggressive breast cancer is associated with poor patient outcome and characterized by the development of tumor cell variants that are able to escape from control of the immune system or are resistant to targeted therapies. The complex molecular mechanisms leading to immune escape and therapy resistance are incompletely understood. We have previously shown that high miR-519a-3p levels are associated with poor survival in breast cancer. Here, we demonstrate that miR-519a-3p confers resistance to apoptosis induced by TRAIL, FasL and granzyme B/perforin by interfering with apoptosis signaling in breast cancer cells...
August 3, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28771104/-atypical-car-t-cells-nkg2d-and-erb-b-as-examples-of-natural-receptor-ligands-to-target-recalcitrant-solid-tumors
#13
David E Gilham, John Maher
Chimeric antigen receptor (CAR) T-cell therapy has recently been recommended for approval for certain B-cell malignancies bringing the approach closer to mainstream cancer treatment. This rapid rise to prominence has been driven by impressive clinical results and the means to successfully commercialize the approach now being actively pursued. The current success of CAR T cells in B-cell malignancies relies upon the absolute lineage specificity of the CD19 antigen. CARs can also be targeted using non-antibody approaches, including the use of receptors and ligands to provide target specificity that have different specificities and binding kinetics...
August 2017: Immunotherapy
https://www.readbyqxmd.com/read/28673007/cytokine-induced-killer-cell-therapy-for-modulating-regulatory-t-cells-in-patients-with-non-small-cell-lung-cancer
#14
Baodan Yu, Junli Wang, Chen He, Wei Wang, Jianli Tang, Runhui Zheng, Chengzhi Zhou, Huanhuan Zhang, Zhiping Fu, Qiasheng Li, Jun Xu
Previous studies have reported that regulatory T cells (Tregs), which are physiologically engaged in the maintenance of immunological self-tolerance, have a critical role in the regulation of the antitumor immune response. Targeting Tregs has the potential to augment cancer vaccine approaches. The current study therefore aimed to evaluate the role of cytokine-induced killer (CIK) cell infusion in modulating Tregs in patients with non-small cell lung cancer (NSCLC). A total of 15 patients with advanced NSCLC were treated by an infusion of CIK cells derived from autologous peripheral blood mononuclear cells (PBMCs)...
July 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28659311/memory-t-cells-expressing-an-nkg2d-car-efficiently-target-osteosarcoma-cells
#15
Lucía Fernández, Jean-Yves Metais, Adela Escudero, María Vela, Jaime Valentín, Isabel Vallcorba, Alejandra Leivas, Juan Torres, Antonio Valeri, Ana Patiño-García, Joaquín Martínez, Wing Leung, Antonio Pérez-Martínez
Purpose: NKG2D ligands (NKG2DL) are expressed on various tumor types and immunosuppressive cells within tumor microenvironments, providing suitable targets for cancer therapy. Various immune cells express NKG2D receptors, including natural killer (NK) cells and CD8+ T cells. Interactions between NKG2DL and NKG2D receptors are essential for NK-cell elimination of osteosarcoma tumor-initiating cells. In this report, we used NKG2D-NKG2DL interactions to optimize an immunotherapeutic strategy against osteosarcoma...
October 1, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28615524/interleukin-15-stimulates-natural-killer-cell-mediated-killing-of-both-human-pancreatic-cancer-and-stellate-cells
#16
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 4th 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)...
May 25, 2017: Oncotarget
https://www.readbyqxmd.com/read/28560327/antibody-mediated-neutralization-of-soluble-mic-significantly-enhances-ctla4-blockade-therapy
#17
Jingyu Zhang, Dai Liu, Guangfu Li, Kevin F Staveley-O'Carroll, Julie N Graff, Zihai Li, Jennifer D Wu
Antibody therapy targeting cytotoxic T lymphocyte-associated antigen 4 (CTLA4) elicited survival benefits in cancer patients; however, the overall response rate is limited. In addition, anti-CTLA4 antibody therapy induces a high rate of immune-related adverse events. The underlying factors that may influence anti-CTLA4 antibody therapy are not well defined. We report the impact of a cancer-derived immune modulator, the human-soluble natural killer group 2D (NKG2D) ligand sMIC (soluble major histocompatibility complex I chain-related molecule), on the therapeutic outcome of anti-CTLA4 antibody using an MIC transgenic spontaneous TRAMP (transgenic adenocarcinoma of the mouse prostate)/MIC tumor model...
May 2017: Science Advances
https://www.readbyqxmd.com/read/28550492/microrna-889-is-downregulated-by-histone-deacetylase-inhibitors-and-confers-resistance-to-natural-killer-cytotoxicity-in-hepatocellular-carcinoma-cells
#18
Haitao Xie, Qiugui Zhang, Hui Zhou, Jun Zhou, Ji Zhang, Yan Jiang, Jinghong Wang, Xianglin Meng, Leping Zeng, Xiaoxin Jiang
Major histocompatibility complex class I chain-related gene B (MICB) is expressed on tumor cells and participates in natural killer (NK) cell-mediated antitumor immune response through engagement with the NKG2D receptor. This study was undertaken to identify novel microRNA (miRNA) regulators of MICB and clarify their functions in NK cell-mediated cytotoxicity to hepatocellular carcinoma (HCC) cells. Bioinformatic analysis and luciferase reporter assay were conducted to search for MICB-targeting miRNAs. Overexpression and knockdown experiments were performed to determine the roles of candidate miRNAs in the susceptibility of HCC cells to NK lysis...
April 2018: Cytotechnology
https://www.readbyqxmd.com/read/28452850/sunitinib-induces-nk-%C3%AE%C2%BAb-dependent-nkg2d-ligand-expression-in-nasopharyngeal-carcinoma-and-hepatoma-cells
#19
Yu-Xian Huang, Xin-Tong Chen, Kun-Yuan Guo, Yu-Hua Li, Bing-Yi Wu, Chao-Yang Song, Yan-Jie He
Multitargeted tyrosine kinase inhibitors (MTKIs) have been shown to combine with natural killer (NK) cell adoptive transfer for the treatment in various cancers. MTKIs sensitize cancer cells to NK cell therapy through upregulation of nature killer group 2 member D ligands (NKG2DLs) on tumor cells. However, the molecular mechanism of MTKIs-mediated upregulation of NKG2DLs is still unknown. In this study, we confirmed sunitinib induced downregulation of its targets, such as vascular endothelial growth factor, platelet-derived growth factor, and c-kit in multiple-drug-resistant nasopharyngeal carcinoma cell line CNE2/DDP and hepatoma cell line HepG2...
June 2017: Journal of Immunotherapy
https://www.readbyqxmd.com/read/28443091/natural-killer-group-2d-ligand-depletion-reconstitutes-natural-killer-cell-immunosurveillance-of-head-and-neck-squamous-cell-carcinoma
#20
Sandra Weil, Stefanie Memmer, Axel Lechner, Volker Huppert, Ariane Giannattasio, Tamara Becker, Andreas Müller-Runte, Karen Lampe, Dirk Beutner, Alexander Quaas, Ralf Schubert, Eva Herrmann, Alexander Steinle, Ulrike Koehl, Lutz Walter, Michael S von Bergwelt-Baildon, Joachim Koch
Head and neck squamous cell carcinoma (HNSCC) is a highly heterogeneous and aggressive tumor originating from the epithelial lining of the upper aero-digestive tract accounting for 300,000 annual deaths worldwide due to failure of current therapies. The natural killer group 2D (NKG2D) receptors on natural killer (NK) cells and several T cell subsets play an important role for immunosurveillance of HNSCC and are thus targeted by tumor immune evasion strategies in particular by shedding of various NKG2D ligands (NKG2DLs)...
2017: Frontiers in Immunology
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