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https://read.qxmd.com/read/30755812/a-novel-cd7-chimeric-antigen-receptor-modified-nk-92mi-cell-line-targeting-t-cell-acute-lymphoblastic-leukemia
#1
Fengtao You, Yinyan Wang, Licui Jiang, Xuejun Zhu, Dan Chen, Lei Yuan, Gangli An, Huimin Meng, Lin Yang
Chimeric antigen receptor (CAR) immunotherapy has recently shown promise in clinical trials for B-cell malignancies; however, designing CARs for T-cell based diseases remain a challenge since most target antigens are shared between normal and malignant cells, leading to CAR-T cell fratricide. CD7 is highly expressed in T-cell acute lymphoblastic leukemia (T-ALL), but it is not expressed in one small group of normal T lymphocytes. Here, we constructed monovalent CD7-CAR-NK-92MI and bivalent dCD7-CAR-NK-92MI cells using the CD7 nanobody VHH6 sequences from our laboratory...
2019: American Journal of Cancer Research
https://read.qxmd.com/read/30734584/preclinical-assessment-of-suitable-natural-killer-nk-cell-sources-for-chimeric-antigen-receptor-car-nk-based-off-the-shelf-aml-immunotherapies
#2
Stephan Klöß, Olaf Oberschmidt, Julia Dahlke, Xuan-Khang Vu, Christine Neudoerfl, Arnold Kloos, Tanja Gardlowski, Nadine Matthies, Michael Heuser, Johann Meyer, Martin Sauer, Christine Falk, Ulrike Koehl, Axel Schambach, Michael A Morgan
The introduction of chimeric antigen receptors (CARs) to augment the anti-cancer activity of immune cells represents one of the major clinical advances in recent years. In this work, we demonstrate that sorted CAR-NK cells have improved anti-leukemia activity as compared to control NK cells that lack a functional CAR. However, in terms of viability, effectiveness, risk of side effects, and clinical practicality and applicability, an important question is whether gene-modified NK cell lines represent better CAR effector cells than primary human donor CAR-NK (CAR-dNK) cells...
February 8, 2019: Human Gene Therapy
https://read.qxmd.com/read/30717444/characterization-of-a-novel-third-generation-anti-cd24-car-against-ovarian-cancer
#3
Rüdiger Klapdor, Shuo Wang, Michael Morgan, Thilo Dörk, Ulrich Hacker, Peter Hillemanns, Hildegard Büning, Axel Schambach
Novel therapeutic approaches against ovarian cancer (OC) are urgently needed because of its high rate of recurrence even after extensive surgery and multi-agent chemotherapy. We aimed to develop a novel anti-CD24 chimeric antigen receptor (CAR) as an immunotherapeutic approach against OC cells and cancer stem cells (CSC). CSC represents a subpopulation of the tumor characterized by enhanced chemoresistance as well as the increased capability of self-renewal and metastasis. We designed a codon-optimized third-generation CAR containing the highly active single chain variable fragment (scFv) "SWA11" against CD24...
February 3, 2019: International Journal of Molecular Sciences
https://read.qxmd.com/read/30685121/natural-killer-cells-for-cancer-immunotherapy-a-new-car-is-catching-up
#4
EDITORIAL
(no author information available yet)
No abstract text is available yet for this article.
January 2019: EBioMedicine
https://read.qxmd.com/read/30665853/nk-cells-specifically-tcr-dressed-to-kill-cancer-cells
#5
Nadia Mensali, Pierre Dillard, Michael Hebeisen, Susanne Lorenz, Theodossis Theodossiou, Marit Renée Myhre, Anne Fåne, Gustav Gaudernack, Gunnar Kvalheim, June Helen Myklebust, Else Marit Inderberg, Sébastien Wälchli
BACKGROUND: Adoptive T-cell transfer of therapeutic TCR holds great promise to specifically kill cancer cells, but relies on modifying the patient's own T cells ex vivo before injection. The manufacturing of T cells in a tailor-made setting is a long and expensive process which could be resolved by the use of universal cells. Currently, only the Natural Killer (NK) cell line NK-92 is FDA approved for universal use. In order to expand their recognition ability, they were equipped with Chimeric Antigen Receptors (CARs)...
January 18, 2019: EBioMedicine
https://read.qxmd.com/read/30651290/nk-cells-expressing-a-chimeric-activating-receptor-eliminate-mdscs-and-rescue-impaired-car-t-cell-activity-against-solid-tumors
#6
Robin Parihar, Charlotte H Rivas, Mai Huynh, Bilal Omer, Natalia Lapteva, Leonid S Metelitsa, Stephen Gottschalk, Cliona M Rooney
Solid tumors are refractory to cellular immunotherapies in part because they contain suppressive immune effectors such as myeloid‑derived suppressor cells (MDSCs) that inhibit cytotoxic lymphocytes. Strategies to reverse the suppressive tumor microenvironment (TME) should also attract and activate immune effectors with antitumor activity. To address this need, we developed gene‑modified natural killer (NK) cells bearing a chimeric receptor in which the activating receptor NKG2D is fused to the cytotoxic z-chain of the T-cell receptor (NKG2D...
January 16, 2019: Cancer Immunology Research
https://read.qxmd.com/read/30646574/natural-killer-cells-and-current-applications-of-chimeric-antigen-receptor-modified-nk-92-cells-in-tumor-immunotherapy
#7
REVIEW
Jianguang Zhang, Huifang Zheng, Yong Diao
Natural killer (NK) cells are innate immune cells that can be activated rapidly to target abnormal and virus-infected cells without prior sensitization. With significant advancements in cell biology technologies, many NK cell lines have been established. Among these cell lines, NK-92 cells are not only the most widely used but have also been approved for clinical applications. Additionally, chimeric antigen receptor-modified NK-92 cells (CAR-NK-92 cells) have shown strong antitumor effects. In this review, we summarize established human NK cell lines and their biological characteristics, and highlight the applications of NK-92 cells and CAR-NK-92 cells in tumor immunotherapy...
January 14, 2019: International Journal of Molecular Sciences
https://read.qxmd.com/read/30628504/adoptive-cell-therapy-for-acute-myeloid-leukemia
#8
Hongbing Ma, Swaminathan Padmanabhan Iyer, Simrit Parmar, Yuping Gong
Acute myeloid leukemia (AML) is the most common tumor in adult patients, most of the patients have a poor prognosis even after high-intensity chemotherapy, especially for relapsed, refractory or elderly patients. Therefore, new methods are needed to change the outcomes. In recent years, an increasing number of immune-therapies are emerging where adoptive cell therapy, a special immunotherapy, has become a promising strategy for AML. Here, we review the clinical application and advancement of donor lymphocyte infusion, chimeric-antigen receptor (CAR) T cell therapy, natural killer (NK) cell therapy and dendritic cell vaccination for AML, hopefully providing an overview of clinical aspects of advances in adoptive cell therapy for AML...
January 10, 2019: Leukemia & Lymphoma
https://read.qxmd.com/read/30613939/advances-in-cellular-and-humoral-immunotherapy-implications-for-the-treatment-of-poor-risk-childhood-adolescent-and-young-adult-b-cell-non-hodgkin-lymphoma
#9
REVIEW
Yaya Chu, Aliza Gardenswartz, Amanda M Termuhlen, Mitchell S Cairo
Patients with relapsed, refractory or advanced stage B non-Hodgkin lymphoma (NHL) continue to have a dismal prognosis. This review summarises current and novel cellular and immunotherapy for these high-risk populations, including haematopoietic stem cell transplant, bispecific antibodies, viral-derived cytotoxic T cells, chimeric antigen receptor (CAR) T cells, and natural killer (NK) cell therapy, as discussed at the 6th International Symposium on Childhood, Adolescent and Young Adult Non-Hodgkin Lymphoma on September 26th-29th 2018 in Rotterdam, the Netherlands, and explores the future of NK/CAR NK therapies...
January 6, 2019: British Journal of Haematology
https://read.qxmd.com/read/30611869/development-of-innate-immune-cells-from-human-pluripotent-stem-cells
#10
Davide Bernarreggi, Somayeh Pouyanfard, Dan S Kaufman
Mouse and human pluripotent stem cells have been widely used to study the development of the hematopoietic and immune systems. Although not all cells can be derived with the same efficiency, immune cells such as natural killer (NK) cells and macrophages can be easily produced from PSCs to enable development of new cell-based therapies. NK cells and macrophages are part of the innate immune system, the first line of defense against malignancies and infectious disease. Human embryonic stem cell (hESC)- and induced pluripotent stem cell (iPSC)-derived NK cells can be produced at a clinical scale suitable for translation into clinical trials...
January 4, 2019: Experimental Hematology
https://read.qxmd.com/read/30591446/culturing-the-human-natural-killer-cell-line-nk-92-in-interleukin-2-and-interleukin-15-implications-for-clinical-trials
#11
Heidi Törnroos, Henry Hägerstrand, Christer Lindqvist
BACKGROUND/AIM: The human natural killer cell line NK-92 is increasingly being used in adoptive cell immunotherapies, either in vitro or in animal models transduced with different chimeric antigen receptor (CAR) constructs. Herein, NK-92 cells were analyzed with respect to their proliferation and cytotoxicity, in the presence of interleukin-2 (IL-2) and interleukin-15 (IL-15). MATERIALS AND METHODS: A time-resolved fluorometric assay (TDA-labeled K562 target cells) was used for measuring the cytotoxic activity of NK-92 cells treated with IL-2, IL-4, IL-7 and/or IL-15...
January 2019: Anticancer Research
https://read.qxmd.com/read/30563208/cellular-immunotherapy-of-canine-cancer
#12
REVIEW
Selamawit Addissie, Hans Klingemann
Infusions with immune cells, such as lymphocytes or natural killer (NK) cells, represent one of several modalities of immunotherapy. In human patients with advanced B-cell leukemia or lymphoma, infusions with chimeric antigen receptor (CAR) T-lymphocytes have shown promising responses. However, the scientific and clinical development of cell-based therapies for dogs, who get cancer of similar types as humans, is lagging behind. One reason is that immune cells and their functionality in dogs are less well characterized, largely due a lack of canine-specific reagents to detect surface markers, and specific cytokines to isolate and expand their immune cells...
December 6, 2018: Veterinary Sciences
https://read.qxmd.com/read/30553527/immunotherapy-in-acute-myeloid-leukemia-and-myelodysplastic-syndromes-the-dawn-of-a-new-era
#13
REVIEW
Yuxin Liu, Jan Philipp Bewersdorf, Maximilian Stahl, Amer M Zeidan
Immunotherapy has revolutionized therapy in both solid and liquid malignancies. The ability to cure acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) with an allogeneic hematopoietic stem cell transplant (HSCT) is proof of concept for the application of immunotherapy in AML and MDS. However, outside of HSCT, only the anti-CD33 antibody drug conjugate gemtuzumab ozogamicin is currently approved as an antibody-targeted therapy for AML. Several avenues of immunotherapeutic drugs are currently in different stages of clinical development...
December 5, 2018: Blood Reviews
https://read.qxmd.com/read/30546945/dnax-activating-protein-10-co-stimulation-enhances-the-anti-tumor-efficacy-of-chimeric-antigen-receptor-t-cells
#14
Ruocong Zhao, Lin Cheng, Zhiwu Jiang, Xinru Wei, Baiheng Li, Qiting Wu, Suna Wang, Simiao Lin, Youguo Long, Xuchao Zhang, Yilong Wu, Xin Du, Duanqing Pei, Pentao Liu, Yangqiu Li, Shuzhong Cui, Yao Yao, Peng Li
Chimeric antigen receptor (CAR) T cell immunotherapies have shown remarkable efficacy in treating multiple types of hematological malignancies but are not sufficiently effective at treating solid tumors. NKG2D is a strong activating receptor for NK cells and a co-stimulatory receptor for T cells. NKG2D signal transduction depends on DNAX-activating protein 10 (DAP10). Here, we introduced the cytoplasmic domain of DAP10 into the second-generation CARs M28z and G28z to generate M28z10 and G28z10, which target mesothelin (MSLN) and glypican 3 (GPC3), respectively...
2019: Oncoimmunology
https://read.qxmd.com/read/30514403/purinergic-targeting-enhances-immunotherapy-of-cd73-solid-tumors-with-piggybac-engineered-chimeric-antigen-receptor-natural-killer-cells
#15
Jiao Wang, Kyle B Lupo, Andrea M Chambers, Sandro Matosevic
BACKGROUND: The anti-tumor immunity of natural killer (NK) cells can be paralyzed by the CD73-induced generation of immunosuppressive adenosine from precursor ATP within the hypoxic microenvironment of solid tumors. In an effort to redirect purinergic immunosuppression of NK cell anti-tumor function, we showed, for the first time, that immunometabolic combination treatment with NKG2D-engineered CAR-NK cells alongside blockade of CD73 ectonucleotidase activity can result in significant anti-tumor responses in vivo...
December 4, 2018: Journal for Immunotherapy of Cancer
https://read.qxmd.com/read/30487575/selective-expansion-of-myeloid-and-nk-cells-in-humanized-mice-yields-human-like-vaccine-responses
#16
Florian Douam, Carly G K Ziegler, Gabriela Hrebikova, Bruno Fant, Robert Leach, Lance Parsons, Wei Wang, Jenna M Gaska, Benjamin Y Winer, Brigitte Heller, Alex K Shalek, Alexander Ploss
Mice engrafted with components of a human immune system have become widely-used models for studying aspects of human immunity and disease. However, a defined methodology to objectively measure and compare the quality of the human immune response in different models is lacking. Here, by taking advantage of the highly immunogenic live-attenuated yellow fever virus vaccine YFV-17D, we provide an in-depth comparison of immune responses in human vaccinees, conventional humanized mice, and second generation humanized mice...
November 28, 2018: Nature Communications
https://read.qxmd.com/read/30410941/combination-therapy-with-epcam-car-nk-92-cells-and-regorafenib-against-human-colorectal-cancer-models
#17
Qing Zhang, Haixu Zhang, Jiage Ding, Hongyan Liu, Huizhong Li, Hailong Li, Mengmeng Lu, Yangna Miao, Liantao Li, Junnian Zheng
Adoptive chimeric antigen receptor-modified T or NK cells (CAR-T or CAR-NK) offer new options for cancer treatment. CAR-T therapy has achieved encouraging breakthroughs in the treatment of hematological malignancies. However, their therapeutic efficacy against solid tumors is limited. New regimens, including combinations with chemical drugs, need to be studied to enhance the therapeutic efficacy of CAR-T or NK cells for solid tumors. An epithelial cell adhesion molecule- (EpCAM-) specific second-generation CAR was constructed and transduced into NK-92 cells by lentiviral vectors...
2018: Journal of Immunology Research
https://read.qxmd.com/read/30367191/-what-is-established-in-cell-therapies-possibilities-and-limits-in-immuno-oncology
#18
REVIEW
A Quaiser, U Köhl
Cell and gene therapy as part of immuno-oncology has reached an important milestone in medicine. After decades of experience stem cell transplantation is well established with worldwide >1 million transplantations to date. Due to the improved success of the last years using chimeric antigen receptor (CAR) T cells for CD19 positive leukemia and lymphomas, the interest in cellular therapies is continuously increasing. The current review also gives a short overview about donor lymphocytes, antigen-specific T cells, regulatory T cells, natural killer (NK) cells, mesenchymal stromal cells and induced pluripotent stem (iPS) cells in immuno-oncology...
December 2018: Der Internist
https://read.qxmd.com/read/30361801/off-the-shelf-cell-therapy-with-induced-pluripotent-stem-cell-derived-natural-killer-cells
#19
REVIEW
Michelle L Saetersmoen, Quirin Hammer, Bahram Valamehr, Dan S Kaufman, Karl-Johan Malmberg
Cell therapy is emerging as a very promising therapeutic modality against cancer, spearheaded by the clinical success of chimeric antigen receptor (CAR) modified T cells for B cell malignancies. Currently, FDA-approved CAR-T cell products are based on engineering of autologous T cells harvested from the patient, typically using a central manufacturing facility for gene editing before the product can be delivered to the clinic and infused to the patients. For a broader implementation of advanced cell therapy and to reduce costs, it would be advantageous to use allogeneic "universal" cell therapy products that can be stored in cell banks and provided upon request, in a manner analogous to biopharmaceutical drug products...
October 25, 2018: Seminars in Immunopathology
https://read.qxmd.com/read/30347240/2b4-cd244-slamf4-and-cs1-cd319-slamf7-in-systemic-lupus-erythematosus-and-cancer
#20
REVIEW
Joseph D Malaer, Armando M Marrufo, Porunelloor A Mathew
Signaling Lymphocyte Activation Molecule (SLAM) family receptors are expressed on different types of hematopoietic cells and play important role in immune regulation in health and disease. 2B4 (CD244, SLAMF4) and CS1 (CD319, CRACC, SLAMF7) were originally identified as NK cell receptors regulating NK cell cytolytic activity. 2B4 is expressed on all NK cells, a subpopulation of T cells, monocytes and basophils. Unlike other activating and inhibitory receptors, 2B4 (CD244) interaction with its ligand CD48 has been shown to mediate both activating and inhibitory functions...
October 19, 2018: Clinical Immunology: the Official Journal of the Clinical Immunology Society
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