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Adoptive T cell therapy

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https://www.readbyqxmd.com/read/27914701/il-2-anti-il-2-complexes-ameliorate-lupus-nephritis-by-expansion-of-cd4-cd25-foxp3-regulatory-t%C3%A2-cells
#1
Ji-Jing Yan, Jae-Ghi Lee, Joon Young Jang, Tai Yeon Koo, Curie Ahn, Jaeseok Yang
Adoptive transfer of regulatory T cells (Tregs) can delay disease progression and reduce mortality in lupus-prone mice. Here, we tested whether complex (IL-2C) consisting of IL-2 and anti-IL-2 monoclonal antibody (JES6-1) ameliorates lupus nephritis by expanding Tregs as an alternative to problematic Treg infusion therapy. IL-2C treatment of NZB/W F1 mice induced an effective and sustained expansion of CD4(+)CD25(+)Foxp3(+) Tregs in both the kidneys and spleen along with decreased renal infiltration of T cells, B cells, and innate immune cells...
November 30, 2016: Kidney International
https://www.readbyqxmd.com/read/27913530/cytokine-release-syndrome-with-novel-therapeutics-for-acute-lymphoblastic-leukemia
#2
Noelle V Frey, David L Porter
T-cell-engaging immunotherapies are exciting new approaches to treat patients with acute lymphoblastic leukemia (ALL). These unique agents, which include blinatumomab, a CD3/CD19 bispecific antibody, and chimeric antigen receptor (CAR) modified T cells targeted to CD19 have shown unprecedented remission rates in the relapsed, refractory ALL setting. Cytokine release syndrome (CRS), resulting from the high magnitude of immune activation by these therapies, is the most significant treatment-related toxicity. CRS manifests with fever and malaise and can progress to life-threatening capillary leak with hypoxia and hypotension...
December 2, 2016: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/27911371/development-of-stem-cell-derived-antigen-specific-regulatory-t-cells-against-autoimmunity
#3
Mohammad Haque, Kristin Fino, Praneet Sandhu, Jianxun Song
Autoimmune diseases arise due to the loss of immunological self-tolerance. Regulatory T cells (Tregs) are important mediators of immunologic self-tolerance. Tregs represent about 5 - 10% of the mature CD4(+) T cell subpopulation in mice and humans, with about 1 - 2% of those Tregs circulating in the peripheral blood. Induced pluripotent stem cells (iPSCs) can be differentiated into functional Tregs, which have a potential to be used for cell-based therapies of autoimmune diseases. Here, we present a method to develop antigen (Ag)-specific Tregs from iPSCs (i...
November 8, 2016: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/27911363/generation-of-induced-pluripotent-stem-cells-from-human-melanoma-tumor-infiltrating-lymphocytes
#4
Hidehito Saito, Kumiko Iwabuchi, Noemi Fusaki, Fumito Ito
Adoptive transfer of ex vivo expanded autologous tumor-infiltrating lymphocytes (TILs) can mediate durable and complete responses in significant subsets of patients with metastatic melanoma. Major obstacles of this approach are the reduced viability of transferred T cells, caused by telomere shortening, and the limited number of TILs obtained from patients. Less-differentiated T cells with long telomeres would be an ideal T cell subset for adoptive T cell therapy;however, generating large numbers of these less-differentiated T cells is problematic...
November 11, 2016: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/27910767/immunostimulatory-effects-of-melphalan-and-usefulness-in-adoptive-cell-therapy-with-antitumor-cd4-t-cells
#5
Michal Kuczma, Zhi-Chun Ding, Gang Zhou
The alkylating agent melphalan is used in the treatment of hematological malignancies, especially multiple myeloma. In the past, the usefulness of melphalan has been solely attributed to its cytotoxicity on fastgrowing cancerous cells. Although the immunomodulatory effects of melphalan were suggested many years ago, only recently has this aspect of melphalan's activity begun to be elucidated at the molecular level. Emerging evidence indicates that melphalan can foster an immunogenic microenvironment by inducing immunogenic cell death (ICD) as characterized by membrane translocation of endoplasmic reticulum protein calreticulin (CRT) and by release of chromatin-binding protein high-mobility group box 1 (HMGB1)...
2016: Critical Reviews in Immunology
https://www.readbyqxmd.com/read/27908931/filling-the-tank-keeping-antitumor-t-cells-metabolically-fit-for-the-long-haul
#6
REVIEW
Greg M Delgoffe
Discoveries in tumor immunology and subsequent clinical advances in cancer immunotherapy have revealed that the immune system is not oblivious to tumor progression but heavily interacts with developing neoplasia and malignancy. A major factor preventing immune destruction is the establishment of a highly immunosuppressive tumor microenvironment (TME), which provides architecture to the tumor, supports indirect means of immunosuppression such as the recruitment of tolerogenic cells like regulatory T cells and myeloid-derived suppressor cells (MDSC), and represents a zone of metabolically dearth conditions...
December 2016: Cancer Immunology Research
https://www.readbyqxmd.com/read/27903296/factors-affecting-long-term-efficacy-of-t-regulatory-cell-based-therapy-in-type-1-diabetes
#7
Natalia Marek-Trzonkowska, Małgorzata Myśliwiec, Dorota Iwaszkiewicz-Grześ, Mateusz Gliwiński, Ilona Derkowska, Magdalena Żalińska, Maciej Zieliński, Marcelina Grabowska, Hanna Zielińska, Karolina Piekarska, Anna Jaźwińska-Curyłło, Radosław Owczuk, Agnieszka Szadkowska, Krystyna Wyka, Piotr Witkowski, Wojciech Młynarski, Przemysława Jarosz-Chobot, Artur Bossowski, Janusz Siebert, Piotr Trzonkowski
BACKGROUND: Recent studies suggest that immunotherapy using T regulatory cells (Tregs) prolongs remission in type 1 diabetes (T1DM). Here, we report factors that possibly affect the efficacy of this treatment. METHODS: The metabolic and immune background of 12 children with recently diagnosed T1DM, as well as that of untreated subjects, during a 2-year follow-up is presented. Patients were treated with up to 30 × 10(6)/kg b.w. of autologous expanded CD3(+)CD4(+)CD25(high)CD127(-) Tregs...
December 1, 2016: Journal of Translational Medicine
https://www.readbyqxmd.com/read/27897332/recent-advances-in-t-cell-immunotherapy-for-haematological-malignancies
#8
REVIEW
Rayne H Rouce, Sandhya Sharma, Mai Huynh, Helen E Heslop
In vitro discoveries have paved the way for bench-to-bedside translation in adoptive T cell immunotherapy, resulting in remarkable clinical responses in a variety of haematological malignancies. Adoptively transferred T cells genetically modified to express CD19 CARs have shown great promise, although many unanswered questions regarding how to optimize T-cell therapies for both safety and efficacy remain. Similarly, T cells that recognize viral or tumour antigens though their native receptors have produced encouraging clinical responses...
November 29, 2016: British Journal of Haematology
https://www.readbyqxmd.com/read/27897048/a-rapid-cell-expansion-process-for-production-of-engineered-autologous-car-t-cell-therapies
#9
Tangying Lily Lu, Omar Pugach, Robert P T Somerville, Steven A Rosenberg, James N Kochenderfer, Marc Better, Steven A Feldman
The treatment of B cell malignancies by adoptive cell transfer (ACT) of anti-CD19 chimeric antigen receptor T cells (CD19 CAR-T) has proven to be a highly successful therapeutic modality in several clinical trials<sup>1-6</sup>. The anti-CD19 CAR T cell production method used to support initial trials relied on numerous manual, open process steps, cell culture media supplemented with human serum and 10 days of cell culture to achieve a clinical dose <sup>7</sup>. This approach limited the ability to support large multicenter clinical trials, as well as scale-up for commercial cell production...
November 29, 2016: Human Gene Therapy Methods
https://www.readbyqxmd.com/read/27895646/manufacturing-natural-killer-cells-as-medicinal-products
#10
REVIEW
Christian Chabannon, Bechara Mfarrej, Sophie Guia, Sophie Ugolini, Raynier Devillier, Didier Blaise, Eric Vivier, Boris Calmels
Natural Killer (NK) cells are innate lymphoid cells (ILC) with cytotoxic and regulatory properties. Their functions are tightly regulated by an array of inhibitory and activating receptors, and their mechanisms of activation strongly differ from antigen recognition in the context of human leukocyte antigen presentation as needed for T-cell activation. NK cells thus offer unique opportunities for new and improved therapeutic manipulation, either in vivo or in vitro, in a variety of human diseases, including cancers...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/27895644/recent-developments-in-cellular-immunotherapy-for-hsct-associated-complications
#11
REVIEW
Monica Reis, Justyna Ogonek, Marsela Qesari, Nuno M Borges, Lindsay Nicholson, Liane Preußner, Anne Mary Dickinson, Xiao-Nong Wang, Eva M Weissinger, Anne Richter
Allogeneic hematopoietic stem cell transplantation is associated with serious complications, and improvement of the overall clinical outcome of patients with hematological malignancies is necessary. During the last decades, posttransplant donor-derived adoptive cellular immunotherapeutic strategies have been progressively developed for the treatment of graft-versus-host disease (GvHD), infectious complications, and tumor relapses. To date, the common challenge of all these cell-based approaches is their implementation for clinical application...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/27892949/the-ebmt-eln-working-group-recommendations-on-the-prophylaxis-and-treatment-of-gvhd-a-change-control-analysis
#12
T Ruutu, A Gratwohl, D Niederwieser, T de Witte, S van der Werf, A van Biezen, M Mohty, N Kröger, A Rambaldi, E McGrath, A Sureda, G Basak, H Greinix, R F Duarte
In 2013, recommendations for a standardized practice in the prophylaxis and treatment of GvHD were adopted and published by the European Society for Blood and Marrow Transplantation and the European LeukemiaNet. One year later, all 341 European Society for Blood and Marrow Transplantation centres performing allogeneic haematopoietic stem cell transplantation were contacted for a change-control analysis and asked to fill in a questionnaire; 111 centres (33%) responded. Of these, 83% had been aware of the recommendations...
November 28, 2016: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/27890259/how-important-is-nk-alloreactivity-and-kir-in-allogeneic-transplantation
#13
REVIEW
Brian C Shaffer, Katharine C Hsu
Relapse of acute myelogenous leukemia (AML) after allogeneic hematopoietic cell transplantation (allo HCT) is a major cause of death in transplant recipients. Efforts to control relapse by promoting donor T-cell alloreactivity, such as withdrawal of immune suppression or donor lymphocyte infusions, are limited by the propensity to induce graft versus host disease (GVHD) and by inadequate efficacy. Therefore, options for AML patients who have relapsed AML after allo HCT are few and outcomes are poor. Similar to T-cells, natural killer (NK) cells have potent anti-leukemia effector capacity, and yet unlike T-cells, NK cells do not mediate GVHD...
December 2016: Best Practice & Research. Clinical Haematology
https://www.readbyqxmd.com/read/27889798/selective-effect-of-cytokine-induced-killer-cells-on-survival-of-patients-with-early-stage-melanoma
#14
Hong Li, Lan Huang, Linbo Liu, Ximei Wang, Zhen Zhang, Dongli Yue, Wei He, Kun Fu, Xueli Guo, Jianmin Huang, Xuan Zhao, Yu Zhu, Liping Wang, Wenjie Dong, Yan Yan, Li Xu, Ming Gao, Shuangning Yang, Yi Zhang
Adoptive immunotherapy using cytokine-induced killer (CIK) cells has shown potential antitumor ability against several kinds of cancers, including melanoma. However, little is known about the achievable outcome of CIK cells in melanoma patients at different pathological stages. Here we recruited 55 patients treated with conventional therapy plus CIK cells as the CIK group, and 49 patients treated with conventional therapy alone as the control group. The pathological characteristics were comparable between two groups, with a follow-up period up to 40 months...
November 26, 2016: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/27887864/optimization-of-cgmp-purification-and-expansion-of-umbilical-cord-blood-derived-t-regulatory-cells-in-support-of-first-in-human-clinical-trials
#15
David H McKenna, Darin Sumstad, Diane M Kadidlo, Bjorn Batdorf, Colin J Lord, Sarah C Merkel, Christine M Koellner, Julie M Curtsinger, Carl H June, James L Riley, Bruce L Levine, Jeffrey S Miller, Claudio G Brunstein, John E Wagner, Bruce R Blazar, Keli L Hippen
BACKGROUND AIMS: Thymic-derived regulatory T cells (tTreg) are critical regulators of the immune system. Adoptive tTreg transfer is a curative therapy for murine models of autoimmunity, graft rejection, and graft-versus-host disease (GVHD). We previously completed a "first-in-human" clinical trial using in vitro expanded umbilical cord blood (UCB)-derived tTreg to prevent GVHD in patients undergoing UCB hematopoietic stem cell transplantation (HSCT). tTreg were safe and demonstrated clinical efficacy, but low yield prevented further dose escalation...
November 22, 2016: Cytotherapy
https://www.readbyqxmd.com/read/27886124/advances-in-cancer-immunotherapy-in-solid-tumors
#16
REVIEW
Smitha Menon, Sarah Shin, Grace Dy
Immunotherapy is heralded as one of the most important advances in oncology. Until recently, only limited immunotherapeutic options were available in selected immunogenic cancers like melanoma and renal cell carcinomas. Nowadays, there is an improved understanding that anti-tumor immunity is controlled by a delicate balance in the tumor microenvironment between immune stimulatory and immune inhibitory pathways. Either by blocking the inhibitory pathways or stimulating the activating pathways that regulate cytotoxic lymphocytes, anti-tumor immunity can be enhanced leading to durable anti-tumor responses...
November 24, 2016: Cancers
https://www.readbyqxmd.com/read/27882353/longitudinal-pet-imaging-demonstrates-biphasic-car-t-cell-responses-in-survivors
#17
Yogindra Vedvyas, Enda Shevlin, Marjan Zaman, Irene M Min, Alejandro Amor-Coarasa, Spencer Park, Susan Park, Keon-Woo Kwon, Turner Smith, Yonghua Luo, Dohyun Kim, Young Kim, Benedict Law, Richard Ting, John Babich, Moonsoo M Jin
Clinical monitoring of adoptive T cell transfer (ACT) utilizes serial blood analyses to discern T cell activity. While useful, these data are 1-dimensional and lack spatiotemporal information related to treatment efficacy or toxicity. We utilized a human genetic reporter, somatostatin receptor 2 (SSTR2), and PET, to quantitatively and longitudinally visualize whole-body T cell distribution and antitumor dynamics using a clinically approved radiotracer. Initial evaluations determined that SSTR2-expressing T cells were detectable at low densities with high sensitivity and specificity...
November 17, 2016: JCI Insight
https://www.readbyqxmd.com/read/27873282/ebv-directed-t-cell-therapeutics-for-ebv-associated-lymphomas
#18
Lauren P McLaughlin, Stephen Gottschalk, Cliona M Rooney, Catherine M Bollard
Epstein Barr virus (EBV) is a human gamma herpes virus that establishes latency in B cells after primary infection. EBV generally only causes a mild, self-limiting viral illness but is also associated with several malignancies including posttransplantation lymphoproliferative disorder in the immunosuppressed host as well as Hodgkin and non-Hodgkin lymphoma in the immune competent host. The expression of EBV antigens by lymphoma has important applications as targets for adoptive T cell therapy. However, as many lymphomas only express subdominant EBV antigens that are less immunogenic, novel strategies are needed to manufacture EBV-specific T cell products specific for Latent Membrane Protein 1 (LMP1) and LMP2, which are expressed in lymphomas with type II and III latency...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27873264/current-trends-and-alternative-scenarios-in-ebv-research
#19
Janos Minarovits, Hans Helmut Niller
Epstein-Barr virus (EBV) infection is associated with several distinct hematological and epithelial malignancies, e.g., Burkitt lymphoma, Hodgkin lymphoma, nasopharyngeal carcinoma, gastric carcinoma, and others. The association with several malignant tumors of local and worldwide distribution makes EBV one of the most important tumor viruses. Furthermore, because EBV can cause posttransplant lymphoproliferative disease, transplant medicine has to deal with EBV as a major pathogenic virus second only to cytomegalovirus...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27872103/rapid-and-continued-t-cell-differentiation-into-long-term-effector-and-memory-stem-cells-in-vaccinated-melanoma-patients
#20
Philippe Gannon, Petra Baumgaertner, Alexandre Huber, Emanuela M Iancu, Laurene Cagnon, Samia Abed-Maillard, Helene Maby-El Hajjami, Daniel E Speiser, Nathalie Rufer
PURPOSE: Cancer patients benefit increasingly from T cell-based therapies, such as adoptive T cell transfer, checkpoint blockade or vaccination. We have previously shown that serial vaccinations with Melan-AMART-126-35 peptide, CpG-B and IFA generated robust tumor-specific CD8 T cell responses in melanoma patients. Here, we describe the detailed kinetics of early- and long-term establishment of T cell frequency, differentiation (into memory and effector cells), poly-functionality and clonotype repertoire induced by vaccination...
November 21, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
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