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nkg2d AND tumor target therapy

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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
#1
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
#2
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
#3
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
#4
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
https://www.readbyqxmd.com/read/27356741/pd1-blockade-enhances-cytotoxicity-of-in-vitro-expanded-natural-killer-cells-towards-myeloma-cells
#5
Yanan Guo, Xiaoli Feng, Yang Jiang, Xiaoyun Shi, Xiangling Xing, Xiaoli Liu, Nailin Li, Bengt Fadeel, Chengyun Zheng
Aiming for an adoptive natural killer (NK) cell therapy, we have developed a novel protocol to expand NK cells from peripheral blood. With this protocol using anti-human CD16 antibody and interleukin (IL)-2, NK (CD3-CD56+) cells could be expanded about 4000-fold with over 70% purity during a 21-day culture. The expanded NK (exNK) cells were shown to be highly cytotoxic to multiple myeloma (MM) cells (RPMI8226) at low NK-target cell ratios. Furthermore, NK cells expanded in the presence of a blocking antibody (exNK+PD1-blockage) against programmed cell death protein-1 (PD1), a key counteracting molecule for NK and T cell activity, demonstrated more potent cytolytic activity against the RPMI8226 than the exNK cells without PD1 blocking...
June 23, 2016: Oncotarget
https://www.readbyqxmd.com/read/27141357/antibody-targeting-soluble-nkg2d-ligand-smic-refuels-and-invigorates-the-endogenous-immune-system-to-fight-cancer
#6
Jennifer Wu
Human tumor-derived soluble NKG2D sMIC paralyzes the immune system through multiple pathways. Targeting soluble MIC with a nonblocking sMIC-neutralizing anti-MIC antibody effectuated and revamped endogenous innate and adoptive antitumor responses. Therapy induced regression of primary tumors and eliminated metastasis in preclinical models.
March 2016: Oncoimmunology
https://www.readbyqxmd.com/read/27096096/natural-killer-cell-immunotherapy-to-target-stem-like-tumor-cells
#7
Steven K Grossenbacher, Robert J Canter, William J Murphy
Advances in cancer immunotherapy are leading to its increasing and successful application for the treatment of solid-tissue cancers. Despite the recent advances there are still significant barriers, in particular, evidence for significant tumor heterogeneity, both genetic and epigenetic that limit long-term efficacy. Subpopulations of "stem-like" tumor cells have been identified in nearly all human malignancies based on both morphologic and functional criteria. Also called cancer stem cells or CSCs, these quiescent cells display enhanced tumorigenic potential and are capable of repopulating tumors in the wake of traditional cytoreductive therapies...
2016: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/26940474/mhc-class-i-chain-related-molecule-a-and-b-expression-is-upregulated-by-cisplatin-and-associated-with-good-prognosis-in-patients-with-non-small-cell-lung-cancer
#8
Riki Okita, Takuro Yukawa, Yuji Nojima, Ai Maeda, Shinsuke Saisho, Katsuhiko Shimizu, Masao Nakata
MHC class I chain-related molecule A and B (MICA/B) are NK group 2 member D (NKG2D) ligands, which are broadly expressed in transformed cells. Both DNA damage-induced ataxia-telangiectasia-mutated (ATM)- and ATM and Rad3-related protein kinases (ATM-ATR) signaling and oncogene-induced PI3K-AKT signaling regulate the expression of NKG2D ligands, which promote NK cell-mediated cytotoxicity via NKG2D-NKG2D ligand interactions. NKG2D ligand overexpression was recently reported to be correlated with good prognosis in several types of cancer...
May 2016: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/26909862/vegfr2-targeted-antibody-fused-with-mica-stimulates-nkg2d-mediated-immunosurveillance-and-exhibits-potent-anti-tumor-activity-against-breast-cancer
#9
Wei Xie, Fang Liu, Youfu Wang, Xueyan Ren, Tong Wang, Zhiguo Chen, Mingying Tang, Fumou Sun, Zhaoting Li, Min Wang, Juan Zhang
Binding of MHC class I-related chain molecules A and B (MICA/B) to the natural killer (NK) cell receptor NK group 2, member D (NKG2D) is thought critical for activating NK-mediated immunosurveillance. Angiogenesis is important for tumor growth and interfering with angiogenesis using the fully human IgG1 anti-VEGFR2 (vascular endothelial growth factor receptor 2) antibody (mAb04) can be effective in treating malignancy. In an effort to make mAb04 more effective we have generated a novel antibody fusion protein (mAb04-MICA) consisting of mAb04 and MICA...
March 29, 2016: Oncotarget
https://www.readbyqxmd.com/read/26625316/cooperative-therapeutic-anti-tumor-effect-of-il-15-agonist-alt-803-and-co-targeting-soluble-nkg2d-ligand-smic
#10
Fahmin Basher, Emily K Jeng, Hing Wong, Jennifer Wu
Shedding of the human NKG2D ligand MIC (MHC class I-chain-related molecule) from tumor cell surfaces correlates with progression of many epithelial cancers. Shedding-derived soluble MIC (sMIC) enables tumor immune escape through multiple immune suppressive mechanisms, such as disturbing natural killer (NK) cell homeostatic maintenance, impairing NKG2D expression on NK cells and effector T cells, and facilitating the expansion of arginase I+ myeloid suppressor cells. Our recent study has demonstrated that sMIC is an effective cancer therapeutic target...
January 5, 2016: Oncotarget
https://www.readbyqxmd.com/read/26472927/tumor-therapeutics-work-as-stress-inducers-to-enhance-tumor-sensitivity-to-natural-killer-nk-cell-cytolysis-by-up-regulating-nkp30-ligand-b7-h6
#11
Guoshuai Cao, Jian Wang, Xiaodong Zheng, Haiming Wei, Zhigang Tian, Rui Sun
Immune cells are believed to participate in initiating anti-tumor effects during regular tumor therapy such as chemotherapy, radiation, hyperthermia, and cytokine injection. One of the mechanisms underlying this process is the expression of so-called stress-inducible immunostimulating ligands. Although the activating receptor NKG2D has been proven to play roles in tumor therapy through targeting its ligands, the role of NKp30, another key activating receptor, is seldom addressed. In this study, we found that the NKp30 ligand B7-H6 was widely expressed in tumor cells and closely correlated to their susceptibility to NK cell lysis...
December 11, 2015: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/26418951/cytokine-induced-killer-cells-efficiently-kill-stem-like-cancer-cells-of-nasopharyngeal-carcinoma-via-the-nkg2d-ligands-recognition
#12
Fang Wei, Xiao-Xiang Rong, Rao-Ying Xie, Li-Ting Jia, Hui-Yan Wang, Yu-Juan Qin, Lin Chen, Hong-Fen Shen, Xiao-Lin Lin, Jie Yang, Sheng Yang, Wei-Chao Hao, Yan Chen, Sheng-Jun Xiao, Hui-Rong Zhou, Tao-Yan Lin, Yu-Shuang Chen, Yan Sun, Kai-Tai Yao, Dong Xiao
Cancer stem cells (CSCs) are considered to be the root cause for cancer treatment failure. Thus, there remains an urgent need for more potent and safer therapies against CSCs for curing cancer. In this study, the antitumor activity of cytokine-induced killer (CIK) cells against putative CSCs of nasopharyngeal carcinoma (NPC) was fully evaluated in vitro and in vivo. To visualize putative CSCs in vitro by fluorescence imaging, and image and quantify putative CSCs in tumor xenograft-bearing mice by in vivo bioluminescence imaging, NPC cells were engineered with CSC detector vector encoding GFP and luciferase (Luc) under control of Nanog promoter...
October 27, 2015: Oncotarget
https://www.readbyqxmd.com/read/26363055/nk-cells-preferentially-target-tumor-cells-with-a-cancer-stem-cell-phenotype
#13
Erik Ames, Robert J Canter, Steven K Grossenbacher, Stephanie Mac, Mingyi Chen, Rachel C Smith, Takeshi Hagino, Jessica Perez-Cunningham, Gail D Sckisel, Shiro Urayama, Arta M Monjazeb, Ruben C Fragoso, Thomas J Sayers, William J Murphy
Increasing evidence supports the hypothesis that cancer stem cells (CSCs) are resistant to antiproliferative therapies, able to repopulate tumor bulk, and seed metastasis. NK cells are able to target stem cells as shown by their ability to reject allogeneic hematopoietic stem cells but not solid tissue grafts. Using multiple preclinical models, including NK coculture (autologous and allogeneic) with multiple human cancer cell lines and dissociated primary cancer specimens and NK transfer in NSG mice harboring orthotopic pancreatic cancer xenografts, we assessed CSC viability, CSC frequency, expression of death receptor ligands, and tumor burden...
October 15, 2015: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/26276724/activated-and-expanded-natural-killer-cells-target-osteosarcoma-tumor-initiating-cells-in-an-nkg2d-nkg2dl-dependent-manner
#14
L Fernández, J Valentín, M Zalacain, W Leung, A Patiño-García, A Pérez-Martínez
Current therapies fail to cure most metastatic or recurrent bone cancer. We explored the efficacy and the pathways involved in natural killer (NK) cells' elimination of osteosarcoma (OS) cells, including tumor initiating cells (TICs), which are responsible for chemotherapy resistance, recurrence, and metastasis. The expression of ligands for NK cell receptors was studied in primary OS cell lines by flow cytometry. In vitro cytotoxicity of activated and expanded NK (NKAE) cells against OS was tested, and the pathways involved explored by using specific antibody blockade...
November 1, 2015: Cancer Letters
https://www.readbyqxmd.com/read/26159925/tlr4-plays-a-crucial-role-in-msc-induced-inhibition-of-nk-cell-function
#15
Ying Lu, Jin Liu, Yang Liu, Yaru Qin, Qun Luo, Quanli Wang, Haifeng Duan
Mesenchymal stem cells (MSC) are a kind of stromal cell within the tumor microenvironment. In our research, MSC derived from acute myeloid leukemia patients' bone marrow (AML-MSC) and lung cancer tissues (LC-MSC) as well as normal bone marrow-derived MSC (BM-MSC) cultured in conditioned medium of HeLa cells were found to have higher expressions of Toll-like receptor (TLR4) mRNA compared with BM-MSC. The sorted TLR4-positive MSC (TLR4+ MSC) differed in cytokine (interleukin-6, interleukin-8, and monocyte chemoattractant protein-1) secretion from those of unsorted MSC...
August 21, 2015: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/26122933/t-cells-engineered-with-chimeric-antigen-receptors-targeting-nkg2d-ligands-display-lethal-toxicity-in-mice
#16
Heather VanSeggelen, Joanne A Hammill, Anna Dvorkin-Gheva, Daniela G M Tantalo, Jacek M Kwiecien, Galina F Denisova, Brian Rabinovich, Yonghong Wan, Jonathan L Bramson
Ligands for the NKG2D receptor are overexpressed on tumors, making them interesting immunotherapy targets. To assess the tumoricidal properties of T cells directed to attack NKG2D ligands, we engineered murine T cells with two distinct NKG2D-based chimeric antigen receptors (CARs): (i) a fusion between the NKG2D receptor and the CD3ζ chain and (ii) a conventional second-generation CAR, where the extracellular domain of NKG2D was fused to CD28 and CD3ζ. To enhance the CAR surface expression, we also engineered T cells to coexpress DAP10...
October 2015: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/26113176/upregulated-expression-of-nkg2d-and-its-ligands-give-potential-therapeutic-targets-for-patients-with-thymoma
#17
X Y Xuan, J F Zhang, G M Hu, Q R Li, P P Liu, Y Du
The activating receptor NKG2D (natural killer group 2, member D) of natural killer (NK) cells promotes tumor immune surveillance by targeting ligands selectively induced on cancer cells, and thus having an important role in antitumor immune response. Because these ligands are not widely expressed on healthy adult tissue, NKG2D ligands may present as useful target for immunotherapeutic approaches in cancer. In this study, to elucidate the role of NKG2D-NKG2D ligand interaction in thymoma tissues and to evaluate the potential role of NKG2D ligands as therapeutic target for thymoma, we examined the expression of NKG2D and its specific ligands: MICA (major histocompatibility complex class I chain-related protein A), MICB (major histocompatibility complex class I chain-related protein B) and ULBP (UL16-binding protein) in 36 thymomas (6 subtype A, 6 subtype AB, 8 subtype B1, 5 subtype B2, 6 subtype B3 and 5 subtype C), 15 thymic atrophy and 8 thymic hyperplasia by immunohistochemistry and reverse transcription-real-time-PCR methods...
July 2015: Cancer Gene Therapy
https://www.readbyqxmd.com/read/26072027/cytomegalovirus-specific-cytokine-induced-killer-cells-concurrent-targeting-of-leukemia-and-cytomegalovirus
#18
Verena Pfirrmann, Sarah Oelsner, Eva Rettinger, Sabine Huenecke, Halvard Bonig, Michael Merker, Winfried S Wels, Jindrich Cinatl, Ralf Schubert, Thomas Klingebiel, Peter Bader
BACKGROUND AIMS: Human cytomegalovirus (CMV) infection and reactivation is a leading complication of allogeneic hematopoietic stem cell transplantation (HSCT). In addition to drug treatment, the adoptive transfer of virus-specific T cells to restore cellular immunity has become a standard therapy after allogeneic HSCT. We recently demonstrated potent anti-leukemic activity of interleukin (IL)-15-activated cytokine-induced killer (CIK) cells. With the use of the same expansion protocol, we asked whether concurrent CMV antigen-pulsing might generate CIK cells with anti-leukemic and anti-CMV activity...
August 2015: Cytotherapy
https://www.readbyqxmd.com/read/26071561/genotoxic-stress-induces-senescence-associated-adam10-dependent-release-of-nkg2d-mic-ligands-in-multiple-myeloma-cells
#19
Alessandra Zingoni, Francesca Cecere, Elisabetta Vulpis, Cinzia Fionda, Rosa Molfetta, Alessandra Soriani, Maria Teresa Petrucci, Maria Rosaria Ricciardi, Daniel Fuerst, Maria Giulia Amendola, Joannis Mytilineos, Cristina Cerboni, Rossella Paolini, Marco Cippitelli, Angela Santoni
Genotoxic stress can promote antitumor NK cell responses by upregulating the surface expression of activating ligands on cancer cells. Moreover, a number of studies suggested a role for soluble NK group 2D ligands in the impairment of NK cell tumor recognition and killing. We investigated whether genotoxic stress could promote the release of NK group 2D ligands (MHC class I-related chain [MIC]A and MICB), as well as the molecular mechanisms underlying this event in human multiple myeloma (MM) cells. Our results show that genotoxic agents used in the therapy of MM (i...
July 15, 2015: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/26029215/revving-up-natural-killer-cells-and-cytokine-induced-killer-cells-against-hematological-malignancies
#20
REVIEW
Gianfranco Pittari, Perla Filippini, Giusy Gentilcore, Jean-Charles Grivel, Sergio Rutella
Natural killer (NK) cells belong to innate immunity and exhibit cytolytic activity against infectious pathogens and tumor cells. NK-cell function is finely tuned by receptors that transduce inhibitory or activating signals, such as killer immunoglobulin-like receptors, NK Group 2 member D (NKG2D), NKG2A/CD94, NKp46, and others, and recognize both foreign and self-antigens expressed by NK-susceptible targets. Recent insights into NK-cell developmental intermediates have translated into a more accurate definition of culture conditions for the in vitro generation and propagation of human NK cells...
2015: Frontiers in Immunology
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