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Natural killer cell immunotherapy

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https://www.readbyqxmd.com/read/29784636/adaptive-nk-cells-resist-regulatory-t-cell-suppression-driven-by-il-37
#1
Dhifaf Sarhan, Keli L Hippen, Amanda Lemire, Skyler Hying, Xianghua Luo, Todd Lenvik, Julie Curtsinger, Zachary Davis, Bin Zhang, Sarah Cooley, Frank Cichocki, Bruce R Blazar, Jeffrey S Miller
Natural Killer (NK) cells are capable of fighting viral infections and cancer. However, these responses are inhibited by immune suppressor cells in the tumor microenvironment. Tumor progression promotes the recruitment and generation of intratumoral regulatory T cells (Tregs), associated with a poor prognosis in cancer patients. Here, we show that canonical NK cells are highly susceptible to Treg-mediated suppression, in contrast to highly resistant CD57+ FcεRγ-NKG2C+ adaptive (CD56+CD3-) NK cells that expand in cytomegalovirus (CMV)-exposed individuals...
May 21, 2018: Cancer Immunology Research
https://www.readbyqxmd.com/read/29780393/immunomodulatory-drugs-exert-anti-leukemia-effects-in-acute-myeloid-leukemia-by-direct-and-immunostimulatory-activities
#2
Aude Le Roy, Thomas Prébet, Rémy Castellano, Armelle Goubard, Florence Riccardi, Cyril Fauriat, Samuel Granjeaud, Audrey Benyamine, Céline Castanier, Florence Orlanducci, Amira Ben Amara, Frédéric Pont, Jean-Jacques Fournié, Yves Collette, Jean-Louis Mege, Norbert Vey, Daniel Olive
Immunomodulatory drugs (IMiDs) are anticancer drugs with immunomodulatory, anti-angiogenesis, anti-proliferative, and pro-apoptotic properties. IMiDs are currently used for the treatment of multiple myeloma, myelodysplastic syndrome, and B-cell lymphoma; however, little is known about efficacy in acute myeloid leukemia (AML). We proposed in this study to investigate the relevance of IMiDs therapy for AML treatment. We evaluated the effect of IMiDs on primary AML blasts ( n  = 24), and the impact in natural killer (NK) cell-mediated immunosurveillance of AML...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29776993/tumor-immune-evasion-arises-through-loss-of-tnf-sensitivity
#3
Conor J Kearney, Stephin J Vervoort, Simon J Hogg, Kelly M Ramsbottom, Andrew J Freeman, Najoua Lalaoui, Lizzy Pijpers, Jessica Michie, Kristin K Brown, Deborah A Knight, Vivien Sutton, Paul A Beavis, Ilia Voskoboinik, Phil K Darcy, John Silke, Joseph A Trapani, Ricky W Johnstone, Jane Oliaro
Immunotherapy has revolutionized outcomes for cancer patients, but the mechanisms of resistance remain poorly defined. We used a series of whole-genome clustered regularly interspaced short palindromic repeat (CRISPR)-based screens performed in vitro and in vivo to identify mechanisms of tumor immune evasion from cytotoxic lymphocytes [CD8+ T cells and natural killer (NK) cells]. Deletion of key genes within the tumor necrosis factor (TNF) signaling, interferon-γ (IFN-γ) signaling, and antigen presentation pathways provided protection of tumor cells from CD8+ T cell-mediated killing and blunted antitumor immune responses in vivo...
May 18, 2018: Science Immunology
https://www.readbyqxmd.com/read/29774202/loss-of-the-cyclin-dependent-kinase-inhibitor-1-in-the-context-of-brachyury-mediated-phenotypic-plasticity-drives-tumor-resistance-to-immune-attack
#4
Duane H Hamilton, Kristen K McCampbell, Claudia Palena
The acquisition of mesenchymal features by carcinoma cells is now recognized as a driver of metastasis and tumor resistance to a range of anticancer therapeutics, including chemotherapy, radiation, and certain small-molecule targeted therapies. With the recent successful implementation of immunotherapies for the treatment of various types of cancer, there is growing interest in understanding whether an immunological approach could be effective at eradicating carcinoma cells bearing mesenchymal features. Recent studies, however, demonstrated that carcinoma cells that have acquired mesenchymal features may also exhibit decreased susceptibility to lysis mediated by immune effector cells, including antigen-specific CD8+ T cells, innate natural killer (NK), and lymphokine-activated killer (LAK) cells...
2018: Frontiers in Oncology
https://www.readbyqxmd.com/read/29773448/the-role-of-the-common-gamma-chain-family-cytokines-in-%C3%AE-%C3%AE-t-cell-based-anti-cancer-immunotherapy
#5
REVIEW
Heleen H Van Acker, Diana Campillo-Davo, Gils Roex, Maarten Versteven, Evelien L Smits, Viggo F Van Tendeloo
Cytokines of the common gamma-chain receptor family, comprising interleukin (IL)-2, IL-4, IL-7, IL-9, IL-15 and IL-21, are vital with respect to organizing and sustaining healthy immune cell functions. Supporting the anti-cancer immune response, these cytokines inspire great interest for their use as vaccine adjuvants and cancer immunotherapies. It is against this background that gamma delta (γδ) T cells, as special-force soldiers and natural contributors of the tumor immunosurveillance, also received a lot of attention the last decade...
May 14, 2018: Cytokine & Growth Factor Reviews
https://www.readbyqxmd.com/read/29770131/real-time-tracking-of-ex-vivo-expanded-natural-killer-cells-toward-human-triple-negative-breast-cancers
#6
Tung Nguyen Thanh Uong, Kyung-Hwa Lee, Sung-Ja Ahn, Kyung Won Kim, Jung-Joon Min, Hoon Hyun, Mee Sun Yoon
Introduction: Ex vivo -expanded natural killer (NK) cells are a potential candidate for cancer immunotherapy based on high cytotoxicity against malignant tumor cells. However, a limited understanding of the migration of activated NK cells toward solid tumors is a critical dilemma in the development of effective and adoptive NK cell-based immunotherapy. Methods: Ex vivo -expanded NK cells from healthy donors were stained with near-infrared fluorophores at different concentrations...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29769573/discovery-of-a-novel-il-15-based-protein-with-improved-developability-and-efficacy-for-cancer-immunotherapy
#7
Qiyue Hu, Xin Ye, Xiangdong Qu, Dongbing Cui, Lei Zhang, Zhibin Xu, Hong Wan, Lianshan Zhang, Weikang Tao
Interleukin-15 (IL-15) can promote both innate and adaptive immune reactions by stimulating CD8+ /CD4+ T cells and natural killer cells (NK) while showing no effect in activating T-regulatory (Treg) cells or inducing activation-associated death among effector T cells and NK cells. Thus, IL-15 is considered as one of the most promising molecules for antitumor immune therapy. To improve the drug-like properties of natural IL-15, we create an IL-15-based molecule, named P22339, with the following characteristics: 1) building a complex of IL-15 and the Sushi domain of IL-15 receptor α chain to enhance the agonist activity of IL-15 via transpresentation; 2) through a rational structure-based design, creating a disulfide bond linking the IL-15/Sushi domain complex with an IgG1 Fc to augment its half-life...
May 16, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29764843/poorly-cytotoxic-terminally-differentiated-cd56-neg-cd16-pos-nk-cells-accumulate-in-kenyan-children-with-burkitt-lymphomas
#8
Catherine S Forconi, Cormac P Cosgrove, Pryia Saikumar-Lakshmi, Christina E Nixon, Joslyn Foley, John Michael Ong'echa, Juliana A Otieno, Galit Alter, Christian Münz, Ann M Moormann
Natural killer (NK) cells are critical for restricting viral infections and mediating tumor immunosurveillance. Epstein-Barr virus (EBV) and Plasmodium falciparum malaria are known risk factors for endemic Burkitt lymphoma (eBL), the most common childhood cancer in equatorial Africa. To date, the composition and function of NK cells have not been evaluated in eBL etiology or pathogenesis. Therefore, using multiparameter flow cytometry and in vitro killing assays, we compared NK cells from healthy children and children diagnosed with eBL in Kenya...
May 22, 2018: Blood Advances
https://www.readbyqxmd.com/read/29764159/emerging-role-of-immunotherapy-for-childhood-cancers
#9
Rupert Handgretinger, Patrick Schlegel
Recent developments in cell and gene therapy have a great impact on the new therapeutic approaches in pediatric cancers. Monoclonal antibodies for neuroblastoma and bispecific antibodies for leukemia have induced significant clinical responses for otherwise chemorefractory patients. Moreover, cellular therapeutic approaches including chimeric antigen receptor (CAR) T-cells as well as natural killer (NK) cells have the potential to cure patients with so far incurable malignancies and are the basis for future new therapies for pediatric cancer...
April 2018: Chinese Clinical Oncology
https://www.readbyqxmd.com/read/29755697/natural-killer-cells-as-a-therapeutic-tool-for-infectious-diseases-current-status-and-future-perspectives
#10
REVIEW
Stanislaw Schmidt, Lars Tramsen, Bushra Rais, Evelyn Ullrich, Thomas Lehrnbecher
Natural Killer (NK) cells are involved in the host immune response against infections due to viral, bacterial and fungal pathogens, all of which are a significant cause of morbidity and mortality in immunocompromised patients. Since the recovery of the immune system has a major impact on the outcome of an infectious complication, there is major interest in strengthening the host response in immunocompromised patients, either by using cytokines or growth factors or by adoptive cellular therapies transfusing immune cells such as granulocytes or pathogen-specific T-cells...
April 17, 2018: Oncotarget
https://www.readbyqxmd.com/read/29755693/exosomes-in-melanoma-a-role-in-tumor-progression-metastasis-and-impaired-immune-system-activity
#11
REVIEW
Marco Tucci, Francesco Mannavola, Anna Passarelli, Luigia Stefania Stucci, Mauro Cives, Franco Silvestris
Exosomes (Exo) are small vesicles produced by melanoma cells and the accessory cells of the tumor microenvironment. They emerge via both classical and direct pathways and actively participate in tumor colonisation of distant tissues. The proteins, nucleic acids, cytokines and growth factors engulfed by Exo are transferred to recipient cells, where they drive numerous functions required for the tumor escape from immune system control and tumor progression. By positively or negatively modulating immune cell properties, Exo provoke immune suppression and, in turn, defective dendritic cell (DC) functions...
April 17, 2018: Oncotarget
https://www.readbyqxmd.com/read/29755647/autologous-tumor-cells-bacillus-calmette-gu%C3%A3-rin-formalin-based-novel-breast-cancer-vaccine-induces-an-immune-antitumor-response
#12
María José Godoy-Calderón, Víctor Salazar, Eglys González-Marcano, Ana Federica Convit
Autologous cancer cell vaccines represent a multivalent patient-specific treatment. Studies have demonstrated that these immunotherapies should be combined with immunomodulators to improve results. We tested in breast cancer the antitumor effects of a 200 µg autologous tumor cells homogenate combined with 0.0625 mg of bacillus Calmette-Guérin (BCG), and 0.02% formalin. We used a 4T1 murine model of BALB/c receiving four weekly injections of either this vaccine or control treatments. The control treatments were either Phosphate Buffer Saline, BCG treated with formalin, or the tumor cells homogenate plus BCG alone...
April 17, 2018: Oncotarget
https://www.readbyqxmd.com/read/29740450/a-novel-three-dimensional-immune-oncology-model-for-high-throughput-testing-of-tumoricidal-activity
#13
Hilary Sherman, Hannah J Gitschier, Ann E Rossi
The latest advancements in oncology research are focused on autologous immune cell therapy. However, the effectiveness of this type of immunotherapy for cancer remediation is not equivalent for all patients or cancer types. This suggests the need for better preclinical screening models that more closely recapitulate in vivo tumor biology. The established method for investigating tumoricidal activity of immunotherapies has been study of two-dimensional (2D) monolayer cultures of immortalized cancer cell lines or primary tumor cells in standard tissue culture vessels...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29737430/hil-15-gene-modified-human-natural-killer-cells-nkl-il15-exhibit-anti-human-leukemia-functions
#14
Wen Jiang, Cai Zhang, Zhigang Tian, Jian Zhang
PURPOSE: Natural killer (NK) cells can kill transformed cells and represent anti-tumor activities for improving the immunotherapy of cancer. In previous works, we established human interleukin-15 (hIL-15) gene-modified NKL cells (NKL-IL15) and demonstrated their efficiency against human hepatocarcinoma cells (HCCs) in vitro and in vivo. To further assess the applicability of NKL-IL15 cells in adoptive cellular immunotherapy for human leukemia, here we report their natural cytotoxicity against leukemia in vitro and in vivo...
May 8, 2018: Journal of Cancer Research and Clinical Oncology
https://www.readbyqxmd.com/read/29733746/the-less-is-more-in-therapeutic-antibodies-afucosylated-anti-cancer-antibodies-with-enhanced-antibody-dependent-cellular-cytotoxicity
#15
Natasha A Pereira, Kah Fai Chan, Pao Chun Lin, Zhiwei Song
Therapeutic monoclonal antibodies are the fastest growing class of biological therapeutics for the treatment of various cancers and inflammatory disorders. In cancer immunotherapy, some IgG1 antibodies rely on the Fc-mediated immune effector function, antibody-dependent cellular cytotoxicity (ADCC), as the major mode of action to deplete tumor cells. It is well-known that this effector function is modulated by the N-linked glycosylation in the Fc region of the antibody. In particular, absence of core fucose on the Fc N-glycan has been shown to increase IgG1 Fc binding affinity to the FcγRIIIa present on immune effector cells such as natural killer cells and lead to enhanced ADCC activity...
May 7, 2018: MAbs
https://www.readbyqxmd.com/read/29733502/natural-killer-cell-immunotherapy-against-multiple-myeloma-progress-and-possibilities
#16
REVIEW
Pan Liu, Yanxia Jin, Haseeb Sattar, Hailing Liu, Weiling Xie, Fuling Zhou
Multiple myeloma (MM) is a complex aggressive mature B-cell malignancy. Although with the wide application of chemotherapy drugs, it remains incurable and the vast majority of patients relapse. Natural killer (NK) cells, also known as CD56+ CD3- large granular lymphocytes, are cytotoxic innate immune cells against MM without prior sensitization steps. NK cell-based immunotherapy is extensively promising in a wide range of clinical settings. It is worthy of note that some novel drugs such as monoclonal antibodies (mAbs), proteasome inhibitors (PIs), and immunomodulators (IMiDs) directly or indirectly activate NK cells to enhance their antitumor activity, and the combined regimens significantly improve the prognosis of MM patients...
May 2018: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/29731862/synergistic-anti-tumor-effects-of-dasatinib-and-dendritic-cell-vaccine-on-metastatic-breast-cancer-in-a-mouse-model
#17
Ningning Song, Hulin Guo, Jia Ren, Suhong Hao, Xinchao Wang
Immunotherapy is currently considered as one of the major anti-tumor modalities, but its efficacy is limited. Dasatinib could improve the expansion and recruitment of cluster of differentiation (CD) 8+ T cells and natural killer (NK) cells to the tumor microenvironment. The present study aimed to evaluate the synergistic anti-tumor effects of dasatinib with dendritic cell (DC) vaccine in metastatic breast cancer. Dasatinib with DC vaccine was administered to mice inoculated with 4T1 breast cancer cells. Thereafter, tumor volume was measured every other day...
May 2018: Oncology Letters
https://www.readbyqxmd.com/read/29717663/runx3-mediated-immune-cell-development-and-maturation
#18
Pal Boto, Tamas Imre Csuth, Istvan Szatmari
The transcription factor RUNX3 is a prominent regulator of multiple hematopoietic cell lineages. Gene loss of function studies demonstrated the unique and essential roles of this master regulator in differentiated lymphoid and myeloid cells. As a complementary approach, RUNX3 was upregulated in various leukocyte subsets to probe the instructive role of this 'multilineage'-specific transcription factor. In this report, we overview the immunomodulatory functions of RUNX3 within the hematopoietic compartment to gain insight into the consequences of Runx3 deletion or overexpression in committed immune cells...
2018: Critical Reviews in Immunology
https://www.readbyqxmd.com/read/29713323/implication-of-interleukin-12-15-18-and-ruxolitinib-in-the-phenotype-proliferation-and-polyfunctionality-of-human-cytokine-preactivated-natural-killer-cells
#19
Iñigo Terrén, Idoia Mikelez, Irati Odriozola, Andrea Gredilla, Javier González, Ane Orrantia, Joana Vitallé, Olatz Zenarruzabeitia, Francisco Borrego
A brief in vitro stimulation of natural killer (NK) cells with interleukin (IL)-12, IL-15, and IL-18 endow them a memory-like behavior, characterized by higher effector responses when they are restimulated after a resting period of time. These preactivated NK cells, also known as cytokine-induced memory-like (CIML) NK cells, have several properties that make them a promising tool in cancer immunotherapy. In the present study, we have described the effect that different combinations of IL-12, IL-15, and IL-18 have on the generation of human CIML NK cells...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29697485/advances-in-the-role-of-the-aryl-hydrocarbon-receptor-to-regulate-early-hematopoietic-development
#20
Mathew G Angelos, Dan S Kaufman
PURPOSE OF REVIEW: We summarize current advances to define the role the aryl hydrocarbon receptor (AHR) plays in mammalian hematopoiesis. We emphasize approaches to modulate AHR throughout human hematopoietic development in vitro to support the production of clinically relevant blood products suitable for patient care. RECENT FINDINGS: Initial data demonstrate that both pharmacologic AHR inhibition and genetic deletion from human pluripotent stem cells provide useful strategies to enhance the yield of hematopoietic stem and progenitor cells...
April 24, 2018: Current Opinion in Hematology
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