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Natural killer cell immunotherapy

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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
#1
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/28943093/naturak-killer-cell-immunotherapies-against-cancer-checkpoint-inhibitors-and-more
#2
REVIEW
Laura Chiossone, Margaux Vienne, Yann M Kerdiles, Eric Vivier
After many years of research, recent advances have shed new light on the role of the immune system in advanced-stage cancer. Various types of immune cells may be useful for therapeutic purposes, along with chemical molecules and engineered monoclonal antibodies. The immune effectors suitable for manipulation for adoptive transfer or drug targeting in vivo include natural killer (NK) cells. These cells are of particular interest because they are tightly regulated by an array of inhibitory and activating receptors, enabling them to kill tumor cells while sparing normal cells...
September 21, 2017: Seminars in Immunology
https://www.readbyqxmd.com/read/28935344/tailoring-natural-killer-cell-immunotherapy-to-the-tumour-microenvironment
#3
REVIEW
Alexander David Barrow, Marco Colonna
Natural killer (NK) cells are cytotoxic and cytokine-secreting cells that can mediate potent anti-tumour activity. Accumulating evidence indicates that NK cell functions are severely compromised within the confines of the tumour microenvironment thus impairing the efficacy and development of NK cell-based therapies. Here we review the various cellular and molecular pathways that tumours have supplanted to evade NK cell surveillance. We highlight novel strategies designed to alleviate or circumvent the immunosuppressive conditions of the tumour microenvironment in order to emancipate NK cell function and stifle the inexorable growth and metastasis of malignant cells...
September 18, 2017: Seminars in Immunology
https://www.readbyqxmd.com/read/28932646/reconstitution-of-multifunctional-cd56-low-cd16-low-natural-killer-cell-subset-in-children-with-acute-leukemia-given-%C3%AE-%C3%AE-t-cell-depleted-hla-haploidentical-haematopoietic-stem-cell-transplantation
#4
Stabile Helena, Nisti Paolo, Peruzzi Giovanna, Fionda Cinzia, Pagliara Daria, Pomonia Brescia Letizia, Merli Pietro, Locatelli Franco, Angela Santoni, Angela Gismondi
We recently described the CD56(low)CD16(low) subset of Natural Killer (NK) cells that both mediate cytotoxic activity and produce IFNγ, being more abundant in bone marrow (BM) than in peripheral blood (PB) of pediatric normal subjects. Given the multifunctional properties of this subset, we examined its development and functional recovery in a cohort of children undergoing α/β T-cell depleted HLA-haploidentical haematopoietic stem cell transplantation (HSCT). The results obtained indicate that CD56(low)CD16(low) NK cells are present in both PB and BM already at one month post-HSCT, with an increased frequency in BM of graft recipients as compared with normal subjects...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28928888/potential-roles-of-peripheral-dopamine-in-tumor-immunity
#5
REVIEW
Xiang Zhang, Qiaofei Liu, Quan Liao, Yupei Zhao
Recent years, immunotherapy has turned out to be a promising strategy against tumors. Peripheral dopamine (DA) has important roles in immune system among tumor patients. Accumulated reports demonstrate variable expression and distribution of DA receptors (DRs) in diverse immune cells. Interestingly, peripheral DA also involves in tumor progression and it exerts anticancer effects on immunomodulation, which includes inflammasomes in cancer, function of immune effector cells, such as T lymphocytes, myeloid-derived suppressor cells (MDSCs), tumor-associated macrophages (TAMs) and natural killer (NK) cells...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28919994/effect-of-entinostat-on-nk-cell-mediated-cytotoxicity-against-osteosarcoma-cells-and-osteosarcoma-lung-metastasis
#6
Simin Kiany, Gangxiong Huang, Eugenie S Kleinerman
There is a crucial need for a new therapeutic approach for osteosarcoma (OS) lung metastasis since this disease remains the main cause of mortality in OS. We previously demonstrated that natural killer (NK) cell therapy has minimal efficacy against OS metastasis. This study determined whether the histone deacetylase inhibitor entinostat could immunosensitize OS cells to NK cell lysis and increases the efficacy of NK cell therapy for OS lung metastasis. Entinostat upregulated ligands for NK cell-activating receptors (major histocompatibility complex [MHC] class I polypeptide-related chain A [MICA] and B [MICB]; UL16 binding proteins 1, 2, 5, and 6; and CD155) on OS cells both in vitro and in vivo and led to more susceptibility to NK cell-mediated cytotoxicity in vitro...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28919991/umbilical-cord-blood-cd34-progenitor-derived-nk-cells-efficiently-kill-ovarian-cancer-spheroids-and-intraperitoneal-tumors-in-nod-scid-il2rg-null-mice
#7
Janneke S Hoogstad-van Evert, Jeannette Cany, Dirk van den Brand, Manon Oudenampsen, Roland Brock, Ruurd Torensma, Ruud L Bekkers, Joop H Jansen, Leon F Massuger, Harry Dolstra
Adoptive transfer of allogeneic natural killer (NK) cells is an attractive therapy approach against ovarian carcinoma. Here, we evaluated the potency of highly active NK cells derived from human CD34+ haematopoietic stem and progenitor cells (HSPC) to infiltrate and mediate killing of human ovarian cancer spheroids using an in vivo-like model system and mouse xenograft model. These CD56+Perforin+ HSPC-NK cells were generated under stroma-free conditions in the presence of StemRegenin-1, IL-15, and IL-12, and exerted efficient cytolytic activity and IFNγ production toward ovarian cancer monolayer cultures...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28919894/potentiation-of-natural-killer-cells-for-cancer-immunotherapy-a-review-of-literature
#8
REVIEW
Lacy E Lowry, William A Zehring
It is widely acknowledged that the human immune system plays a crucial role in preventing the formation and progression of innumerable types of cancer (1). The mechanisms by which this occurs are numerous, including contributions from both the innate and adaptive immune systems. As such, immunotherapy has long been believed to be an auspicious solution in the treatment of malignancy (2). Recent research has highlighted the promise of natural killer (NK) cells as a more directed immunotherapy approach. This paper will focus on the methods of potentiation of NK cells for their use in cancer therapy...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28915900/a-randomized-phase-ii-study-to-assess-the-effect-of-adjuvant-immunotherapy-using-%C3%AE-galcer-pulsed-dendritic-cells-in-the-patients-with-completely-resected-stage-ii-iiia-non-small-cell-lung-cancer-study-protocol-for-a-randomized-controlled-trial
#9
Hideo Saka, Chiyoe Kitagawa, Yukito Ichinose, Mitsuhiro Takenoyama, Hidenori Ibata, Tatsuo Kato, Koji Takami, Motohiro Yamashita, Tadashi Maeda, Sadanori Takeo, Hitoshi Ueda, Kan Okabayashi, Seiji Nagashima, Tadayuki Oka, Hidenori Kouso, Seiichi Fukuyama, Kentaro Yoshimoto, Mototsugu Shimokawa, Akiko M Saito, Suminobu Ito
BACKGROUND: As the toxicity associated with the α-GalCer-pulsed dendritic cell (DC) therapy could be considered to be negligible, its addition to postoperative adjuvant chemotherapy would be expected to greatly improve the therapeutic effect, and could result in prolonged survival. The aim of the present study is to compare the therapeutic efficacy of alpha-galactosylceramide-pulsed DC therapy in patients who have undergone a complete resection of stage II-IIIA non-small-cell lung cancer (NSCLC) followed by postoperative adjuvant therapy with cisplatin plus vinorelbine, to that in patients who did not receive additional treatment (surgical resection plus postoperative adjuvant chemotherapy only)...
September 15, 2017: Trials
https://www.readbyqxmd.com/read/28912774/therapeutic-antibodies-to-kir3dl2-and-other-target-antigens-on-cutaneous-t-cell-lymphomas
#10
REVIEW
Christian Schmitt, Anne Marie-Cardine, Armand Bensussan
KIR3DL2 is a member of the killer cell immunoglobulin-like receptor (KIR) family that was initially identified at the surface of natural killer (NK) cells. KIR3DL2, also known as CD158k, is expressed as a disulfide-linked homodimer. Each chain is composed of three immunoglobulin-like domains and a long cytoplasmic tail containing two immunoreceptor tyrosine-based inhibitory motifs. Beside its expression on NK cells, it is also found on rare circulating T lymphocytes, mainly CD8(+). Although the KIR gene number varies between haplotype, KIR3DL2 is a framework gene present in all individuals...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28904191/the-dose-of-retroviral-infection-determines-the-induction-of-anti-viral-nk-cell-responses
#11
Elisabeth Littwitz-Salomon, Simone Schimmer, Ulf Dittmer
Natural killer (NK) cells are part of the innate immune system and recognize virus-infected cells as well as tumor cells. Conflicting data about the beneficial or even detrimental role of NK cells in different infectious diseases were described. While the type of pathogen strongly influences NK cell functionality, less is known about how the infection dose influences the quality of a NK cell response against retroviruses. Here we used the well-established Friend retrovirus (FV) mouse model to investigate the impact of virus dose on the induction of anti-viral NK cell functions...
September 13, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28903381/tumor-location-impacts-immune-response-in-mouse-models-of-colon-cancer
#12
Xianda Zhao, Lihua Li, Timothy K Starr, Subbaya Subramanian
Existing preclinical models of human colorectal cancer (CRC) that rely on syngeneic subcutaneous grafts are problematic, because of increasing evidence that the immune microenvironment in subcutaneous tissue is significantly different from the gastrointestinal tract. Similarly, existing orthotopic models that use a laparotomy for establishing grafts are also problematic, because the surgical procedure results in extensive inflammation, thereby creating a nonphysiologic tumor microenvironment. To facilitate the bench-to-bedside translation of CRC immunotherapy strategies, we developed a novel orthotopic model in mice that uses endoscopy-guided microinjection of syngeneic cancer cells...
August 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28900509/biodegradable-hollow-mesoporous-silica-nanoparticles-for-regulating-tumor-microenvironment-and-enhancing-antitumor-efficiency
#13
Miao Kong, Jiamin Tang, Qi Qiao, Tingting Wu, Yan Qi, Songwei Tan, Xueqin Gao, Zhiping Zhang
There is accumulating evidence that regulating tumor microenvironment plays a vital role in improving antitumor efficiency. Herein, to remodel tumor immune microenvironment and elicit synergistic antitumor effects, lipid-coated biodegradable hollow mesoporous silica nanoparticle (dHMLB) was constructed with co-encapsulation of all-trans retinoic acid (ATRA), doxorubicin (DOX) and interleukin-2 (IL-2) for chemo-immunotherapy. The nanoparticle-mediated combinational therapy provided a benign regulation on tumor microenvironment through activation of tumor infiltrating T lymphocytes and natural killer cells, promotion of cytokines secretion of IFN-γ and IL-12, and down-regulation of immunosuppressive myeloid-derived suppressor cells, cytokine IL-10 and TGF-β...
2017: Theranostics
https://www.readbyqxmd.com/read/28894585/cell-based-immunotherapy-in-stage-iiia-inflammatory-breast-cancer-with-declining-innate-immunity-following-successive-chemotherapies-a-case-report
#14
Ranganathan Chidambaram, Hiroshi Terunuma, Madasamy Balamurugan, Vidyasagar Devaprasad Dedeepiya, Premkumar Sumana, Rajappa Senthilkumar, Mathaiyan Rajmohan, Ramalingam Karthick, Senthilkumar Preethy, Samuel J K Abraham
Cancer stem cells in breast cancer migrating to the bone marrow may cause future metastasis, particularly during periods of decreased immunity. Natural killer (NK) cells have a role in immune surveillance and are able to target cancer stem cells. The present study reported a case in which NK cell-based autologous immune enhancement therapy was used combined with conventional treatments in a patient with stage IIIA breast cancer, yielding >28 months of disease-free survival. However, there was a gradual decline in the in vitro expansion of NK cells with subsequent chemotherapeutic treatments...
September 2017: Molecular and Clinical Oncology
https://www.readbyqxmd.com/read/28894383/comparison-of-autogeneic-and-allogeneic-natural-killer-cells-immunotherapy-on-the-clinical-outcome-of-recurrent-breast-cancer
#15
Shuzhen Liang, Kecheng Xu, Lizhi Niu, Xiaohua Wang, Yingqing Liang, Mingjie Zhang, Jibing Chen, Mao Lin
In the present study, we aimed to compare the clinical outcome of autogeneic and allogeneic natural killer (NK) cells immunotherapy for the treatment of recurrent breast cancer. Between July 2016 and February 2017, 36 patients who met the enrollment criteria were randomly assigned to two groups: autogeneic NK cells immunotherapy group (group I, n=18) and allogeneic NK cells immunotherapy group (group II, n=18). The clinical efficacy, quality of life, immune function, circulating tumor cell (CTC) level, and other related indicators were evaluated...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28888619/natural-killer-cell-mediated-immunosurveillance-of-human-cancer
#16
REVIEW
Karl-Johan Malmberg, Mattias Carlsten, Andreas Björklund, Ebba Sohlberg, Yenan T Bryceson, Hans-Gustaf Ljunggren
The contribution of natural killer (NK) cells to immunosurveillance of human cancer remains debatable. Here, we discuss advances in several areas of human NK cell research, many of which support the ability of NK cells to prevent cancer development and avoid relapse following adoptive immunotherapy. We describe the molecular basis for NK cell recognition of human tumor cells and provide evidence for NK cell-mediated killing of human primary tumor cells ex vivo. Subsequently, we highlight studies demonstrating the ability of NK cells to migrate to, and reside in, the human tumor microenvironment where selection of tumor escape variants from NK cells can occur...
September 6, 2017: Seminars in Immunology
https://www.readbyqxmd.com/read/28888485/immunobiology-of-the-il-15-il-15r%C3%AE-complex-as-an-antitumor-and-antiviral-agent
#17
REVIEW
Yin Guo, Liming Luan, Naeem K Patil, Edward R Sherwood
Interleukin (IL)-15 is essential for natural killer (NK), NKT and memory (m) CD8(+) T cell development and function, and is currently under investigation as an immunotherapeutic agent for the treatment of cancer. Recently, the creation of IL-15 superagonist by complexing IL-15 and its high affinity receptor alpha (IL-15 Rα) in solution, inspired by the natural trans-presentation of IL-15, advances the potential of IL-15-based tumor immunotherapy. IL-15 superagonist shows promising advantages over monomeric IL-15 such as sustaining high circulating concentrations due to prolonged half-life and more potently stimulating NK and CD8(+) T effector lymphocytes...
September 1, 2017: Cytokine & Growth Factor Reviews
https://www.readbyqxmd.com/read/28883824/natural-killer-nk-cell-education-differentially-influences-hiv-antibody-dependent-nk-cell-activation-and-antibody-dependent-cellular-cytotoxicity
#18
REVIEW
Nicole F Bernard, Zahra Kiani, Alexandra Tremblay-McLean, Sanket A Kant, Christopher E Leeks, Franck P Dupuy
Immunotherapy using broadly neutralizing antibodies (bNAbs) endowed with Fc-mediated effector functions has been shown to be critical for protecting or controlling viral replication in animal models. In human, the RV144 Thai trial was the first trial to demonstrate a significant protection against HIV infection following vaccination. Analysis of the correlates of immune protection in this trial identified an association between the presence of antibody-dependent cellular cytotoxicity (ADCC) mediated by immunoglobulin G (IgG) antibodies (Abs) to HIV envelope (Env) V1/V2 loop structures and protection from infection, provided IgA Abs with competing specificity were not present...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28882429/natural-killer-cells-unleashed-checkpoint-receptor-blockade-and-bike-trike-utilization-in-nk-mediated-anti-tumor-immunotherapy
#19
REVIEW
Zachary B Davis, Daniel A Vallera, Jeffrey S Miller, Martin Felices
Natural killer (NK) cells have long been known to mediate anti-tumor responses without prior sensitization or recognition of specific tumor antigens. However, the tumor microenvironment can suppress NK cell function resulting in tumor escape and disease progression. Despite recent advances in cytokine therapy and NK cell adoptive transfer, tumor expression of ligands to NK - expressed checkpoint receptors can still suppress NK mediated tumor lysis. This review will explore many of the checkpoint receptors tumors utilize to manipulate the NK cell response as well as some of the current and upcoming pharmacological solutions to limit tumor suppression of NK cell function...
September 4, 2017: Seminars in Immunology
https://www.readbyqxmd.com/read/28881567/restoration-of-immune-surface-molecules-in-kaposi-sarcoma-associated-herpes-virus-infected-cells-by-lenalidomide-and-pomalidomide
#20
David A Davis, Suraj Mishra, Holda A Anagho, Ashley I Aisabor, Prabha Shrestha, Victoria Wang, Yuki Takamatsu, Kenji Maeda, Hiroaki Mitsuya, Jerome B Zeldis, Robert Yarchoan
Kaposi sarcoma-associated herpesvirus (KSHV) is the cause of several tumors, including Kaposi sarcoma and primary effusion lymphoma (PEL). Most viruses have evolved means of escaping immune recognition. KSHV downregulates MHC-I expression during lytic infection, and expression of ICAM-1 and B7-2 (CD86) during latent infection, allowing evasion of T cell and natural killer immunity respectively. These effects are largely mediated by two KSHV-encoded proteins, K3 and K5. We show here that lenalidomide (Len) and pomalidomide (Pom) prevent down-regulation of MHC-I during lytic activation, and restore ICAM-1 and B7-2 surface expression in latently infected PEL cells...
August 1, 2017: Oncotarget
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