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https://www.readbyqxmd.com/read/28932644/romidepsin-alone-or-in-combination-with-anti-cd20-chimeric-antigen-receptor-expanded-natural-killer-cells-targeting-burkitt-lymphoma-in-vitro-and-in-immunodeficient-mice
#1
Yaya Chu, Ashlin Yahr, Brian Huang, Janet Ayello, Matthew Barth, Mitchell S Cairo
Facilitating the development of alternative targeted therapeutic strategies is urgently required to improve outcome or circumvent chemotherapy resistance in children, adolescents, and adults with recurrent/refractory de novo mature B-cell (CD20) non-Hodgkin lymphoma, including Burkitt lymphoma (BL). Romidepsin, a histone deacetylase inhibitor (HDACi), has been used to treat cutaneous T-cell lymphoma. We have demonstrated the significant anti-tumor effect of anti-CD20 chimeric antigen receptor (CAR) modified expanded peripheral blood natural killer (exPBNK) against rituximab-sensitive and -resistant BL...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28880014/chimeric-antigen-receptor-car-transduced-natural-killer-cells-in-tumor-immunotherapy
#2
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/28879551/clinical-grade-manufacturing-of-genetically-modified-car-expressing-nk-92-cells-for-the-treatment-of-erbb2-positive-malignancies
#3
Paulina Nowakowska, Annette Romanski, Nicole Miller, Marcus Odendahl, Halvard Bonig, Congcong Zhang, Erhard Seifried, Winfried S Wels, Torsten Tonn
BACKGROUND: The NK-92/5.28.z cell line (also referred to as HER2.taNK) represents a stable, lentiviral-transduced clone of ErbB2 (HER2)-specific, second-generation CAR-expressing derivative of clinically applicable NK-92 cells. This study addresses manufacturing-related issues and aimed to develop a GMP-compliant protocol for the generation of NK-92/5.28.z therapeutic doses starting from a well-characterized GMP-compliant master cell bank. MATERIALS AND METHODS: Commercially available GMP-grade culture media and supplements (fresh frozen plasma, platelet lysate) were evaluated for their ability to support expansion of NK-92/5...
September 6, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28878363/a-tcr-based-chimeric-antigen-receptor
#4
Even Walseng, Hakan Köksal, Ibrahim M Sektioglu, Anne Fåne, Gjertrud Skorstad, Gunnar Kvalheim, Gustav Gaudernack, Else Marit Inderberg, Sébastien Wälchli
Effector T cells equipped with engineered antigen receptors specific for cancer targets have proven to be very efficient. Two methods have emerged: the Chimeric Antigen Receptors (CARs) and T-cell Receptor (TCR) redirection. Although very potent, CAR recognition is limited to membrane antigens which represent around 1% of the total proteins expressed, whereas TCRs have the advantage of targeting any peptide resulting from cellular protein degradation. However, TCRs depend on heavy signalling machinery only present in T cells which restricts the type of eligible therapeutic cells...
September 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28877899/equipping-nk-cells-with-cars
#5
(no author information available yet)
Adding a chimeric antigen receptor (CAR) to natural killer (NK) cells is garnering interest as a therapeutic strategy because this immune cell type doesn't cause graft-versus-host disease, making its widespread, off-the-shelf use feasible. Based on promising preclinical data, a phase I/II trial of one such CAR NK-cell therapy is under way, targeting CD19 in hematologic malignancies.
September 6, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28857616/adoptive-cell-therapy-in-multiple-myeloma
#6
S Vallet, M Pecherstorfer, K Podar
Recent breakthrough advances in Multiple Myeloma (MM) immunotherapy have been achieved with the approval of the first two monoclonal antibodies, elotuzumab and daratumumab. Adoptive cell therapy (ACT) represents yet another, maybe the most powerful modality of immunotherapy, in which allogeneic or autologous effector cells are expanded and activated ex vivo followed by their re-infusion back into patients. Infused effector cells belong to two categories: naturally occurring, non-engineered cells (donor lymphocyte infusion, myeloma infiltrating lymphocytes, deltagamma T cells) or genetically- engineered antigen-specific cells (chimeric antigen receptor T or NK cells, TCR-engineered cells)...
August 31, 2017: Expert Opinion on Biological Therapy
https://www.readbyqxmd.com/read/28838796/nk-cell-based-immunotherapy-for-cancer
#7
REVIEW
Fang Fang, Weihua Xiao, Zhigang Tian
Natural killer (NK) cells can induce an antigen-independent immune response against malignant cells. A growing number of scientific reports and clinical studies have shown promising anti-tumor effects when using NK cell-based immunotherapy. Currently, various approaches are being used to enhance the number and function of NK cells. One approach uses cytokines to selectively boost both the number as well as the efficacy of anti-tumor functions of NK cells. Another emerging approach focuses on checkpoint inhibitors targeting the NK cell receptor...
August 21, 2017: Seminars in Immunology
https://www.readbyqxmd.com/read/28836469/improved-killing-of-ovarian-cancer-stem-cells-by-combining-a-novel-chimeric-antigen-receptor-based-immunotherapy-and-chemotherapy
#8
Rüdiger Klapdor, Shuo Wang, Ulrich Hacker, Hildegard Büning, Michael Morgan, Thilo Dörk, Peter Hillemanns, Axel Schambach
Ovarian cancer represents the most lethal gynecological cancer. Although cytoreductive chemotherapy and surgery lead to complete macroscopic tumor removal, most of the patients in advanced stages suffer from recurrent disease and subsequently die. This may be explained by the activity of cancer stem cells (CSC), which are a subpopulation of cells with an elevated chemoresistance and an increased capacity for self-renewal and metastatic spread. Specifically targeting these cells by adoptive immunotherapy represents a promising strategy to reduce the risk for recurrent disease...
August 24, 2017: Human Gene Therapy
https://www.readbyqxmd.com/read/28810809/optimization-of-human-nk-cell-manufacturing-fully-automated-separation-improved-i-ex-vivo-i-expansion-using-il-21-with-autologous-feeder-cells-and-generation-of-anti-cd123-car-expressing-effector-cells
#9
Stephan Klöß, Olaf Oberschmidt, Michael Morgan, Julia Dahlke, Lubomir Arseniev, Volker Huppert, Markus Granzin, Tanja Gardlowski, Nadine Matthies, Stefanie Soltenborn, Axel Schambach, Ulrike Koehl
BACKGROUND AND AIMS: The administration of ex-vivo expanded Natural killer (NK) cells as potential antitumor effector cells appears to be suitable for effector cell-based immunotherapies in high-risk cancer patients. However, the GMP-conform manufacturing of clinical-grade NK cells at sufficiently high numbers represent a great challenge. Therefore, we improved and optimized previous expansion protocols for those effector cells through the use of newly developed culture medium, IL-21 and autologous feeder cells...
August 16, 2017: Human Gene Therapy
https://www.readbyqxmd.com/read/28771105/nk-92-cell-another-ideal-carrier-for-chimeric-antigen-receptor
#10
Wan-Ning Wang, Guang-Yu Zhou, Wen-Long Zhang
The remarkable clinical outcomes of the treatment for B-cell malignancies through the application of CD19 chimeric antigen receptor T (CAR-T) cells have made adoptive immunotherapy with genetically modified immune effector cells a hotspot in the field of antitumor. However, numerous toxicities of CAR-T cells have been identified. Thus, some studies have resorted to another cytotoxic cell, NK-92 cell, to reach for better efficacy with minimal toxicity. Preclinical studies have confirmed the safety and feasibility of the genetically modified NK-92 cells with highly specific cytotoxicity in vitro and in vivo...
August 2017: Immunotherapy
https://www.readbyqxmd.com/read/28725044/cord-blood-nk-cells-engineered-to-express-il-15-and-a-cd19-targeted-car-show-long-term-persistence-and-potent-antitumor-activity
#11
E Liu, Y Tong, G Dotti, H Shaim, B Savoldo, M Mukherjee, J Orange, X Wan, X Lu, A Reynolds, M Gagea, P Banerjee, R Cai, M H Bdaiwi, R Basar, M Muftuoglu, L Li, D Marin, W Wierda, M Keating, R Champlin, E Shpall, K Rezvani
Chimeric antigen receptors (CARs) have been used to redirect the specificity of autologous T cells against leukemia and lymphoma with promising clinical results. Extending this approach to allogeneic T cells is problematic as they carry a significant risk of graft-versus-host disease (GVHD). Natural killer (NK) cells are highly cytotoxic effectors, killing their targets in a non-antigen-specific manner without causing GVHD. Cord blood (CB) offers an attractive, allogeneic, off-the-self source of NK cells for immunotherapy...
July 20, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28724658/a-daily-dose-of-5-mg-folic-acid-for-90-days-is-associated-with-increased-serum-unmetabolized-folic-acid-and-reduced-natural-killer-cell-cytotoxicity-in-healthy-brazilian-adults
#12
Clovis Paniz, Juliano Felix Bertinato, Maylla Rodrigues Lucena, Eduardo De Carli, Patrícia Mendonça da Silva Amorim, Guilherme Wataru Gomes, Cecília Zanin Palchetti, Maria Stella Figueiredo, Christine M Pfeiffer, Zia Fazili, Ralph Green, Elvira Maria Guerra-Shinohara
Background: The effects of high-dose folic acid (FA) supplementation in healthy individuals on blood folate concentrations and immune response are unknown.Objective: The aim of the study was to evaluate the effects of daily consumption of a tablet containing 5 mg FA on serum folate; number and cytotoxicity of natural killer (NK) cells; mRNA expression of dihydrofolate reductase (DHFR), methylenetetrahydrofolate reductase (MTHFR), interferon γ (IFNG), tumor necrosis factor α (TNFA), and interleukin 8 (IL8) genes; and concentrations of serum inflammatory markers...
September 2017: Journal of Nutrition
https://www.readbyqxmd.com/read/28689001/immuno-oncologic-approaches-car-t-cells-and-checkpoint-inhibitors
#13
REVIEW
Francesca Gay, Mattia D'Agostino, Luisa Giaccone, Mariella Genuardi, Moreno Festuccia, Mario Boccadoro, Benedetto Bruno
Advances in understanding myeloma biology have shown that disease progression is not only the consequence of intrinsic tumor changes but also of interactions between the tumor and the microenvironment in which the cancer grows. The immune system is an important component of the tumor microenvironment in myeloma, and acting on the immune system is an appealing new treatment strategy. There are 2 ways to act toward immune cells and boost antitumor immunity: (1) to increase antitumor activity (acting on T and NK cytotoxic cells), and (2) to reduce immunosuppression (acting on myeloid-derived stem cells and T regulatory cells)...
August 2017: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/28668320/engineering-natural-killer-cells-for-cancer-immunotherapy
#14
REVIEW
Katayoun Rezvani, Rayne Rouce, Enli Liu, Elizabeth Shpall
The past several years have seen tremendous advances in the engineering of immune effector cells as therapy for cancer. While chimeric antigen receptors (CARs) have been used extensively to redirect the specificity of autologous T cells against hematological malignancies with striking clinical results, studies of CAR-modified natural killer (NK) cells have been largely preclinical. In this review, we focus on recent advances in NK cell engineering, particularly on preclinical evidence suggesting that NK cells may be as effective as T cells in recognizing and killing targets after genetic modification...
August 2, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28659311/memory-t-cells-expressing-an-nkg2d-car-efficiently-target-osteosarcoma-cells
#15
Lucía Fernández, Jean-Yves Metais, Adela Escudero, Maria Vela, Jaime Valentín, Isabel Vallcorba, Alejandra Leivas, Juan Torres, Antonio Valeri, Ana Patiño-García, Joaquín Martínez-López, Wing Leung, Antonio Pérez-Martínez
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. We evaluated in vitro and in vivo the safety and cytotoxic capacity against osteosarcoma cells of CD45RA- memory T cells expressing an NKG2D-4-1BB-CD3z chimeric antigen receptor (CAR)...
June 28, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28651074/chimeric-antigen-receptor-engineered-natural-killer-and-natural-killer-t-cells-for-cancer-immunotherapy
#16
REVIEW
Dominique Bollino, Tonya J Webb
Natural killer (NK) cells of the innate immune system and natural killer T (NKT) cells, which have roles in both the innate and adaptive responses, are unique lymphocyte subsets that have similarities in their functions and phenotypes. Both cell types can rapidly respond to the presence of tumor cells and participate in immune surveillance and antitumor immune responses. This has incited interest in the development of novel cancer therapeutics based on NK and NKT cell manipulation. Chimeric antigen receptors (CARs), generated through the fusion of an antigen-binding region of a monoclonal antibody or other ligand to intracellular signaling domains, can enhance lymphocyte targeting and activation toward diverse malignancies...
September 2017: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/28649246/redirected-primary-human-chimeric-antigen-receptor-natural-killer-cells-as-an-off-the-shelf-immunotherapy-for-improvement-in-cancer-treatment
#17
REVIEW
Olaf Oberschmidt, Stephan Kloess, Ulrike Koehl
Primary human natural killer (NK) cells recognize and subsequently eliminate virus infected cells, tumor cells, or other aberrant cells. However, cancer cells are able to develop tumor immune escape mechanisms to undermine this immune control. To overcome this obstacle, NK cells can be genetically modified to express chimeric antigen receptors (CARs) in order to improve specific recognition of cancer surface markers (e.g., CD19, CD20, and ErbB2). After target recognition, intracellular CAR domain signaling (CD3ζ, CD28, 4-1BB, and 2B4) leads to activation of PI3K or DNAX proteins (DAP10, DAP12) and finally to enhanced cytotoxicity, proliferation, and/or interferon γ release...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28572802/chimeric-antigen-receptor-engineered-nk-92-cells-an-off-the-shelf-cellular-therapeutic-for-targeted-elimination-of-cancer-cells-and-induction-of-protective-antitumor-immunity
#18
Congcong Zhang, Pranav Oberoi, Sarah Oelsner, Anja Waldmann, Aline Lindner, Torsten Tonn, Winfried S Wels
Significant progress has been made in recent years toward realizing the potential of natural killer (NK) cells for cancer immunotherapy. NK cells can respond rapidly to transformed and stressed cells and have the intrinsic potential to extravasate and reach their targets in almost all body tissues. In addition to donor-derived primary NK cells, also the established NK cell line NK-92 is being developed for adoptive immunotherapy, and general safety of infusion of irradiated NK-92 cells has been established in phase I clinical trials with clinical responses observed in some of the cancer patients treated...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28539325/cd7-edited-t-cells-expressing-a-cd7-specific-car-for-the-therapy-of-t-cell-malignancies
#19
Diogo Gomes-Silva, Madhuwanti Srinivasan, Sandhya Sharma, Ciaran M Lee, Dimitrios L Wagner, Timothy H Davis, Rayne H Rouce, Gang Bao, Malcolm K Brenner, Maksim Mamonkin
Extending the success of chimeric antigen receptor (CAR) T cells to T-cell malignancies is problematic because most target antigens are shared between normal and malignant cells, leading to CAR T-cell fratricide. CD7 is a transmembrane protein highly expressed in acute T-cell leukemia (T-ALL) and in a subset of peripheral T-cell lymphomas. Normal expression of CD7 is largely confined to T cells and natural killer (NK) cells, reducing the risk of off-target-organ toxicity. Here, we show that the expression of a CD7-specific CAR impaired expansion of transduced T cells because of residual CD7 expression and the ensuing fratricide...
July 20, 2017: Blood
https://www.readbyqxmd.com/read/28494200/a-new-therapeutic-potential-for-cancers-one-car-with-2-different-engines
#20
Abdolkarim Sheikhi, Abdollah Jafarzadeh
Tumor cells escape from immune recognition by several mechanisms such as down-regulating of MHC class I molecules, losing of tumor antigens, etc. The purpose of cancer immunotherapy is to robust or reconstruct the capacity of the immune system to recognize and kill tumor cells by overwhelming the mechanisms by which tumors escape the immune response. One of the novel immunotherapeutic strategies were used to potentiate NK- and T cell functions is chimeric antigen receptor (CAR). CARs are composed of an antigen-binding domain of a molecule such as an antibody (that binds to a tumor associated antigens expressed on the surface of tumor cells) and an intracellular T cell activation domain...
August 3, 2017: Human Vaccines & Immunotherapeutics
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