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https://www.readbyqxmd.com/read/28494200/a-new-therapeutic-potential-for-cancers-one-car-with-2-different-engines
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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
#11
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
https://www.readbyqxmd.com/read/27887866/continuously-expanding-car-nk-92-cells-display-selective-cytotoxicity-against-b-cell-leukemia-and-lymphoma
#12
Sarah Oelsner, Miriam E Friede, Congcong Zhang, Juliane Wagner, Susanne Badura, Peter Bader, Evelyn Ullrich, Oliver G Ottmann, Hans Klingemann, Torsten Tonn, Winfried S Wels
BACKGROUND AIMS: Natural killer (NK) cells can rapidly respond to transformed and stressed cells and represent an important effector cell type for adoptive immunotherapy. In addition to donor-derived primary NK cells, continuously expanding cytotoxic cell lines such as NK-92 are being developed for clinical applications. METHODS: To enhance their therapeutic utility for the treatment of B-cell malignancies, we engineered NK-92 cells by lentiviral gene transfer to express chimeric antigen receptors (CARs) that target CD19 and contain human CD3ζ (CAR 63...
February 2017: Cytotherapy
https://www.readbyqxmd.com/read/27765614/genetically-re-engineered-k562%C3%A2-cells-significantly-expand-and-functionally-activate-cord-blood-natural-killer-cells-potential-for-adoptive-cellular-immunotherapy
#13
Janet Ayello, Jessica Hochberg, Allyson Flower, Yaya Chu, Laxmi V Baxi, William Quish, Carmella van de Ven, Mitchell S Cairo
Natural killer (NK) cells play a significant role in reducing relapse in patients with hematological malignancies after allogeneic stem cell transplantation, but NK cell number and naturally occurring inhibitory signals limit their capability. Interleukin-15 (IL-15) and 4-1BBL are important modulators of NK expansion and functional activation. To overcome these limitations, cord blood mononuclear cells (CB MNCs) were ex vivo expanded for 7 days with genetically modified K562-mbIL15-41BBL (MODK562) or wild-type K562 (WTK562)...
February 2017: Experimental Hematology
https://www.readbyqxmd.com/read/27655849/cytokine-induced-memory-like-natural-killer-cells-exhibit-enhanced-responses-against-myeloid-leukemia
#14
Rizwan Romee, Maximillian Rosario, Melissa M Berrien-Elliott, Julia A Wagner, Brea A Jewell, Timothy Schappe, Jeffrey W Leong, Sara Abdel-Latif, Stephanie E Schneider, Sarah Willey, Carly C Neal, Liyang Yu, Stephen T Oh, Yi-Shan Lee, Arend Mulder, Frans Claas, Megan A Cooper, Todd A Fehniger
Natural killer (NK) cells are an emerging cellular immunotherapy for patients with acute myeloid leukemia (AML); however, the best approach to maximize NK cell antileukemia potential is unclear. Cytokine-induced memory-like NK cells differentiate after a brief preactivation with interleukin-12 (IL-12), IL-15, and IL-18 and exhibit enhanced responses to cytokine or activating receptor restimulation for weeks to months after preactivation. We hypothesized that memory-like NK cells exhibit enhanced antileukemia functionality...
September 21, 2016: Science Translational Medicine
https://www.readbyqxmd.com/read/27653295/21st-nantes-actualit%C3%A3-s-transplantation-when-stem-cells-meet-immunology
#15
Ignacio Anegon, Tuan Huy Nguyen
"When Stem Cells Meet Immunology" has been the topic of the 21st annual "Nantes Actualités en Transplantation" meeting (June 9-10, 2016, Nantes, France). This meeting brought together pioneers and leading experts in the fields of stem cells, biomaterials and immunoregulation. Presentations covered multipotent (mesenchymal and hematopoietic) and pluripotent stem cells (embryonic and induced) for regenerative medicine of incurable diseases, immunotherapy and blood transfusions. An additional focus had been immune rejections and responses of allogeneic or autologous stem cells...
January 2017: Transplantation
https://www.readbyqxmd.com/read/27530534/interactions-between-natural-killer-cells-and-dendritic-cells-favour-t-helper1-type-responses-to-bcg-in-calves
#16
Carly A Hamilton, Suman Mahan, Gary Entrican, Jayne C Hope
Vaccination of neonatal calves with BCG induces a significant level of protection from infection with Mycobacterium bovis, the causative agent of bovine tuberculosis. Since neonatal vaccination of humans with BCG induces activation of NK cells, and young calves have high circulating numbers of these cells, we hypothesised that NK cells are important in the protective response to BCG. Furthermore, since NK cells play a role in shaping adaptive immune responses through interactions with DCs, we investigated the interactions between NK cells and DCs in the context of BCG...
2016: Veterinary Research
https://www.readbyqxmd.com/read/27496866/cd137-stimulation-enhances-cetuximab-induced-natural-killer-dendritic-cell-priming-of-antitumor-t-cell-immunity-in-patients-with-head-and-neck-cancer
#17
Raghvendra M Srivastava, Sumita Trivedi, Fernando Concha-Benavente, Sandra P Gibson, Carly Reeder, Soldano Ferrone, Robert L Ferris
PURPOSE: Cetuximab, an EGFR-specific antibody (mAb), modestly improves clinical outcome in patients with head and neck cancer (HNC). Cetuximab mediates natural killer (NK) cell:dendritic cell (DC) cross-talk by cross-linking FcγRIIIa, which is important for inducing antitumor cellular immunity. Cetuximab-activated NK cells upregulate the costimulatory receptor CD137 (4-1BB), which, when triggered by agonistic mAb urelumab, might enhance NK-cell functions, to promote T-cell-based immunity...
February 1, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27494836/novel-anti-cd3-chimeric-antigen-receptor-targeting-of-aggressive-t-cell-malignancies
#18
Kevin H Chen, Masayuki Wada, Amelia E Firor, Kevin G Pinz, Alexander Jares, Hua Liu, Huda Salman, Marc Golightly, Fengshuo Lan, Xun Jiang, Yupo Ma
Peripheral T-cell lymphomas (PTCLS) comprise a diverse group of difficult to treat, very aggressive non-Hodgkin's lymphomas (NHLS) with poor prognoses and dismal patient outlook. Despite the fact that PTCLs comprise the majority of T-cell malignancies, the standard of care is poorly established. Chimeric antigen receptor (CAR) immunotherapy has shown in B-cell malignancies to be an effective curative option and this extends promise into treating T-cell malignancies. Because PTCLS frequently develop from mature T-cells, CD3 is similarly strongly and uniformly expressed in many PTCL malignancies, with expression specific to the hematological compartment thus making it an attractive target for CAR design...
August 30, 2016: Oncotarget
https://www.readbyqxmd.com/read/27322989/trikes-and-bikes-join-cars-on-the-cancer-immunotherapy-highway
#19
Szun Szun Tay, Hernan Carol, Maté Biro
Unprecedented clinical success has recently been achieved in cancer immunotherapy using cytotoxic T cells armed with activating tumor-specific Chimeric Antigen Receptors (CARs). Natural killer (NK) cells, potent cytotoxic effectors, also hold potential to be effectively harnessed for immunotherapy. The anti-tumor efficacy of NK cell therapies has been limited by a lack of antigen specificity and the poor persistence of NK cells in vivo. To address these limitations, Vallera and colleagues developed novel Trispecific Killer cell Engagers (TriKEs), reported in the Feb...
November 2016: Human Vaccines & Immunotherapeutics
https://www.readbyqxmd.com/read/27253354/chimeric-antigen-receptor-engineered-cytokine-induced-killer-cells-overcome-treatment-resistance-of-pre-b-cell-acute-lymphoblastic-leukemia-and-enhance-survival
#20
Sarah Oelsner, Juliane Wagner, Miriam E Friede, Verena Pfirrmann, Sabrina Genßler, Eva Rettinger, Christian J Buchholz, Heike Pfeifer, Ralf Schubert, Oliver G Ottmann, Evelyn Ullrich, Peter Bader, Winfried S Wels
Pre-emptive cancer immunotherapy by donor lymphocyte infusion (DLI) using cytokine-induced killer (CIK) cells may be beneficial to prevent relapse with a reduced risk of causing graft-versus-host-disease. CIK cells are a heterogeneous effector cell population including T cells (CD3(+) CD56(-) ), natural killer (NK) cells (CD3(-) CD56(+) ) and natural killer T (T-NK) cells (CD3(+) CD56(+) ) that exhibit non-major histocompatibility complex (MHC)-restricted cytotoxicity and are generated by ex vivo expansion of peripheral blood mononuclear cells in the presence of interferon (IFN)-γ, anti-CD3 antibody, interleukin-2 (IL-2) and interleukin-15 (IL-15)...
October 15, 2016: International Journal of Cancer. Journal International du Cancer
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