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nkg2d AND tumor target therapy

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https://www.readbyqxmd.com/read/29147621/in-depth-immunophenotyping-of-patients-with-glioblastoma-multiforme-impact-of-steroid-treatment
#1
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
#2
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 NK cell adoptive transfer with hypomethylating agents (HMA) is an attractive therapeutic approach for patients with acute myeloid leukemia (AML). However, data regarding the impact of HMA on NK cell functionality are mostly derived from in vitro studies with high non-clinical relevant drug concentrations. Here, we report a comparative study of azacitidine and decitabine 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...
November 14, 2017: 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
#3
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/28915646/interleukin-15-stimulates-natural-killer-cell-mediated-killing-of-both-human-pancreatic-cancer-and-stellate-cells
#4
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
#5
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...
September 7, 2017: 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
#6
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
#7
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
#8
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
#9
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...
June 28, 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
#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 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
#11
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
#12
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...
May 26, 2017: Cytotechnology
https://www.readbyqxmd.com/read/28452850/sunitinib-induces-nk-%C3%AE%C2%BAb-dependent-nkg2d-ligand-expression-in-nasopharyngeal-carcinoma-and-hepatoma-cells
#13
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
#14
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
https://www.readbyqxmd.com/read/28203118/human-u87-glioblastoma-cells-with-stemness-features-display-enhanced-sensitivity-to-natural-killer-cell-cytotoxicity-through-altered-expression-of-nkg2d-ligand
#15
Se-Jeong Oh, Jung-In Yang, Ok Kim, Eun-Jung Ahn, Woo Dae Kang, Jae-Hyuk Lee, Kyung-Sub Moon, Kyung-Hwa Lee, Duck Cho
BACKGROUND: Glioblastoma (GBM) is one of the most lethal tumors with a poor prognosis. Its inevitable recurrence is frequently explained by the presence of cancer stem cells. We aimed to show that human GBM cells with stemness features are more sensitive to natural killer (NK) cells than GBM cells without stemness characteristics. METHODS: Natural killer cell cytotoxicity was measured using flow cytometry in neurosphere-forming U87 GBM cells cultured with neurobasal media (NBE condition) and compared with that in serum-cultured U87 GBM cells (serum condition)...
2017: Cancer Cell International
https://www.readbyqxmd.com/read/28123600/activation-or-suppression-of-the-immune-response-mediators-in-biliary-tract-cancer-btc-patients-a-systematic-review-and-meta-analysis
#16
Ying Wang, Min Ding, Qian Zhang, Jinghan Wang, Xijing Yang, Fuping Zhou, Linfang Li, Zhengang Yuan, Huajun Jin, Qijun Qian
Background: Infiltration of immune cells and immune microenvironment determine the proliferative activity of the tumor and metastasis. The aim of this study was to analyze the influence of activation or suppression of the immune response mediators on the prognosis of biliary tract cancer (BTC). Methods: We searched Pubmed, Web of Science, Embase and The Cochrane Library for relevant literatures until June 2016. The quality of studies was assessed by QUADAS-2 and NOS tools. Forest and funnel plots and all statistical analyses were generated by using Review Manager 5...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/27903272/inhibition-of-bromodomain-and-extra-terminal-bet-proteins-increases-nkg2d-ligand-mica-expression-and-sensitivity-to-nk-cell-mediated-cytotoxicity-in-multiple-myeloma-cells-role-of-cmyc-irf4-mir-125b-interplay
#17
Maria Pia Abruzzese, Maria Teresa Bilotta, Cinzia Fionda, Alessandra Zingoni, Alessandra Soriani, Elisabetta Vulpis, Cristiana Borrelli, Beatrice Zitti, Maria Teresa Petrucci, Maria Rosaria Ricciardi, Rosa Molfetta, Rossella Paolini, Angela Santoni, Marco Cippitelli
BACKGROUND: Anti-cancer immune responses may contribute to the control of tumors after conventional chemotherapy, and different observations have indicated that chemotherapeutic agents can induce immune responses resulting in cancer cell death and immune-stimulatory side effects. Increasing experimental and clinical evidence highlight the importance of natural killer (NK) cells in immune responses toward multiple myeloma (MM), and combination therapies able to enhance the activity of NK cells against MM are showing promise in treating this hematologic cancer...
December 1, 2016: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/27671170/combination-treatment-with-decitabine-and-ionizing-radiation-enhances-tumor-cells-susceptibility-of-t-cells
#18
Cheol-Hun Son, Hong-Rae Lee, Eun-Kyoung Koh, Dong-Yeok Shin, Jae-Ho Bae, Kwangmo Yang, You-Soo Park
Decitabine has been found to have anti-metabolic and anti-tumor activities in various tumor cells. Recently, the use of decitabine in combination with other conventional therapies reportedly resulted in improved anti-tumor activity against various tumors. Ionizing radiation (IR) is widely used as a cancer treatment. Decitabine and IR improve immunogenicity and susceptibility of tumor cells to immune cells by up-regulating the expression of various molecules such as major histocompatibility complex (MHC) class I; natural-killer group 2, member D (NKG2D) ligands; and co-stimulatory molecules...
September 27, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27551071/precision-glycocalyx-editing-as-a-strategy-for-cancer-immunotherapy
#19
Han Xiao, Elliot C Woods, Petar Vukojicic, Carolyn R Bertozzi
Cell surface sialosides constitute a central axis of immune modulation that is exploited by tumors to evade both innate and adaptive immune destruction. Therapeutic strategies that target tumor-associated sialosides may therefore potentiate antitumor immunity. Here, we report the development of antibody-sialidase conjugates that enhance tumor cell susceptibility to antibody-dependent cell-mediated cytotoxicity (ADCC) by selective desialylation of the tumor cell glycocalyx. We chemically fused a recombinant sialidase to the human epidermal growth factor receptor 2 (HER2)-specific antibody trastuzumab through a C-terminal aldehyde tag...
September 13, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27467923/adam10-new-selective-inhibitors-reduce-nkg2d-ligand-release-sensitizing-hodgkin-lymphoma-cells-to-nkg2d-mediated-killing
#20
Maria Raffaella Zocchi, Caterina Camodeca, Elisa Nuti, Armando Rossello, Roberta Venè, Francesca Tosetti, Irene Dapino, Delfina Costa, Alessandra Musso, Alessandro Poggi
Hodgkin lymphoma (HL) resistant to conventional therapies is increasing, making of interest the search for new schemes of treatment. Members of the "A Disintegrin And Metalloproteases" (ADAMs) family, mainly ADAM10 or ADAM17, have been proposed as therapeutic targets in solid tumors and some ADAMs inhibitors have been shown to exert antitumor effects. We have previously described an overexpression of ADAM10 in HL, together with increased release of NKG2D ligands (NKG2D-L) and reduced activation of effector T lymphocytes with anti-lymphoma capacity...
May 2016: Oncoimmunology
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