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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-anti-tumor-activity
#1
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.(1-3) 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
#2
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...
July 19, 2017: Journal of Nutrition
https://www.readbyqxmd.com/read/28689001/immuno-oncologic-approaches-car-t-cells-and-checkpoint-inhibitors
#3
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)...
June 17, 2017: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/28668320/engineering-natural-killer-cells-for-cancer-immunotherapy
#4
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...
June 28, 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
#5
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
#6
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...
June 9, 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
#7
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
#8
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
#9
Diogo Gomes-Silva, Madhuwanti Srinivasan, Sandhya Sharma, Ciaran M Lee, Timothy H Davis, Rayne H Rouce, Gang Bao, Malcolm K Brenner, Maksim Mamonkin
Extending the success of CAR T cells to T-cell malignancies is problematic since 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- and 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 due to residual CD7 expression and the ensuing fratricide...
May 24, 2017: Blood
https://www.readbyqxmd.com/read/28494200/a-new-therapeutic-potential-for-cancers-one-car-with-2-different-engines
#10
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...
May 11, 2017: Human Vaccines & Immunotherapeutics
https://www.readbyqxmd.com/read/28488245/chimeric-antigen-receptor-car-modified-natural-killer-cell-based-immunotherapy-and-immunological-synapse-formation-in-cancer-and-hiv
#11
REVIEW
Dongfang Liu, Shuo Tian, Kai Zhang, Wei Xiong, Ndongala Michel Lubaki, Zhiying Chen, Weidong Han
Cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells contribute to the body's immune defenses. Current chimeric antigen receptor (CAR)-modified T cell immunotherapy shows strong promise for treating various cancers and infectious diseases. Although CAR-modified NK cell immunotherapy is rapidly gaining attention, its clinical applications are mainly focused on preclinical investigations using the NK92 cell line. Despite recent advances in CAR-modified T cell immunotherapy, cost and severe toxicity have hindered its widespread use...
May 9, 2017: Protein & Cell
https://www.readbyqxmd.com/read/28428885/the-why-what-and-how-of-the-new-fact-standards-for-immune-effector-cells
#12
EDITORIAL
Marcela V Maus, Sarah Nikiforow
Novel cellular therapies outside of traditional hematopoietic stem cell transplantation or hematopoietic progenitor cell (HPC) therapy are currently under evaluation in clinical trials across the United States and around the world. Several cellular products, e.g., CD19-directed Chimeric Antigen Receptor (CAR) T cells, are poised for FDA approval and thus increased use at a wider range of academic centers within the next year, with the likelihood of dissemination to standard oncology practice once safety is confirmed...
2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28321815/immune-therapy-for-sarcomas
#13
Peter M Anderson
Absolute lymphocyte count (ALC) recovery rapidly occurring at 14 days after start of chemotherapy for osteosarcoma and Ewing sarcoma is a good prognostic factor. Conversely, lymphopenia is associated with significantly decreased sarcoma survival. Clearly, the immune system can contribute towards better survival from sarcoma. This chapter will describe treatment and host factors that influence immune function and how effective local control and systemic interventions of sarcoma therapy can cause inflammation and/or immune suppression but are currently the standard of care...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28321811/interleukin-2-old-and-new-approaches-to-enhance-immune-therapeutic-efficacy
#14
Pooja Dhupkar, Nancy Gordon
Interleukin-2 (IL-2) is a very well-known cytokine that has been studied for the past 35 years. It plays a major role in the growth and proliferation of many immune cells such NK and T cells. It is an important immunotherapy cytokine for the treatment of various diseases including cancer. Systemic delivery of IL-2 has shown clinical benefit in renal cell carcinoma and melanoma patients. However, its use has been limited by the numerous toxicities encountered with the systemic delivery. Intravenous IL-2 causes the well-known "capillary leak syndrome," or the leakage of fluid from the circulatory system to the interstitial space resulting in hypotension (low blood pressure), edema, and dyspnea that can lead to circulatory shock and eventually cardiopulmonary collapse and multiple organ failure...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28236305/autologous-lymphapheresis-for-the-production-of-chimeric-antigen-receptor-t%C3%A2-cells
#15
Elizabeth S Allen, David F Stroncek, Jiaqiang Ren, Anne F Eder, Kamille A West, Terry J Fry, Daniel W Lee, Crystal L Mackall, Cathy Conry-Cantilena
BACKGROUND: The first step in manufacturing chimeric antigen receptor (CAR) T cells is to collect autologous CD3+ lymphocytes by apheresis. Patients, however, often have leukopenia or have other disease-related complications. We evaluated the feasibility of collecting adequate numbers of CD3+ cells, risk factors for inadequate collections, and the rate of adverse events. STUDY DESIGN AND METHODS: Apheresis lymphocyte collections from patients participating in three CAR T-cell clinical trials were reviewed...
May 2017: Transfusion
https://www.readbyqxmd.com/read/28197367/targeting-ewing-sarcoma-with-activated-and-gd2-specific-chimeric-antigen-receptor-engineered-human-nk-cells-induces-upregulation-of-immune-inhibitory-hla-g
#16
Sareetha Kailayangiri, Bianca Altvater, Christian Spurny, Silke Jamitzky, Sonja Schelhaas, Andreas H Jacobs, Constanze Wiek, Katharina Roellecke, Helmut Hanenberg, Wolfgang Hartmann, Heinz Wiendl, Susann Pankratz, Jutta Meltzer, Nicole Farwick, Lea Greune, Maike Fluegge, Claudia Rossig
Activated and in vitro expanded natural killer (NK) cells have substantial cytotoxicity against many tumor cells, but their in vivo efficacy to eliminate solid cancers is limited. Here, we used chimeric antigen receptors (CARs) to enhance the activity of NK cells against Ewing sarcomas (EwS) in a tumor antigen-specific manner. Expression of CARs directed against the ganglioside antigen GD2 in activated NK cells increased their responses to GD2+ allogeneic EwS cells in vitro and overcame resistance of individual cell lines to NK cell lysis...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28074066/preclinical-targeting-of-aggressive-t-cell-malignancies-using-anti-cd5-chimeric-antigen-receptor
#17
K H Chen, M Wada, K G Pinz, H Liu, K-W Lin, A Jares, A E Firor, X Shuai, H Salman, M Golightly, F Lan, L Senzel, E L Leung, X Jiang, Y Ma
The outlook for T-cell malignancies remain poor due to the lack of effective therapeutic options. Chimeric antigen receptor (CAR) immunotherapy has recently shown promise in clinical trials for B-cell malignancies, however, designing CARs for T-cell based disease remain a challenge due to the shared surface antigen pool between normal and malignant T-cells. Normal T-cells express CD5 but NK (natural killer) cells do not, positioning NK cells as attractive cytotoxicity cells for CD5CAR design. Additionally, CD5 is highly expressed in T-cell acute lymphoblastic leukemia (T-ALL) and peripheral T-cell lymphomas (PTCLs)...
February 10, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28063176/frequency-and-phenotype-of-natural-killer-cells-and-natural-killer-cell-subsets-in-bovine-lymphoid-compartments-and-blood
#18
Carly A Hamilton, Suman Mahan, Charlotte R Bell, Bernardo Villarreal-Ramos, Bryan Charleston, Gary Entrican, Jayne C Hope
Natural killer (NK) cells are widely distributed in lymphoid and non-lymphoid tissues, but little is known about the recirculation of NK cells between blood and tissues. This is relevant to understanding recirculation in the steady-state and also for determining the roles for NK cells in vaccine-induced immunity and responses to infection. Therefore, the percentage of NK cells and their phenotype across peripheral blood, afferent lymph and lymph nodes in steady-state conditions was investigated in cattle using the pseudo-afferent lymphatic cannulation model...
May 2017: Immunology
https://www.readbyqxmd.com/read/28025936/current-status-of-leukemia-cytotherapy-exploitation-with-immune-cells
#19
REVIEW
Haiyan Bao, Depei Wu
With the development of chemotherapy and hematopoietic stem cell transplantation (HSCT), the prognosis of leukemia patients has been improved greatly in the past few decades. However, relapsed and refractory leukemia is still the major cause of mortality in leukemia patients. Besides, advancing age, poor performance status and severe co-morbidities limit the applicability of cytotoxic chemotherapy in certain groups of leukemia patients. Novel agents including nucleoside analogs, kinase inhibitors targeting oncoproteins and monoclonal antibodies are under investigation for the management of leukemia...
2017: Current Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28011441/cannabinoid-receptors-on-peripheral-leukocytes-from-patients-with-schizophrenia-evidence-for-defective-immunomodulatory-mechanisms
#20
Salvina Maria de Campos-Carli, Marcio Sobreira Araújo, Amanda Cardoso de Oliveira Silveira, Vitor Bortolo de Rezende, Natalia Pessoa Rocha, Rodrigo Ferretjans, Rafael Ribeiro-Santos, Andrea Teixeira-Carvalho, Olindo Assis Martins-Filho, Michael Berk, João Vinícius Salgado, Antonio Lucio Teixeira
OBJECTIVES: to evaluate cannabinoid receptors (CBRs) expression on peripheral immune cells, i.e., blood monocytes, neutrophils, lymphocytes, and NK cells, and their relationship to a wide range of serum cytokine levels in subjects with schizophrenia and controls. METHODS: A sample of 55 people with chronic schizophrenia and 48 controls were enrolled in the study. The expression of the cannabinoid receptors CB1R and CB2R was evaluated in peripheral blood leukocytes by flow cytometry...
December 3, 2016: Journal of Psychiatric Research
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