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https://www.readbyqxmd.com/read/27911371/development-of-stem-cell-derived-antigen-specific-regulatory-t-cells-against-autoimmunity
#1
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
#2
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
#3
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
#4
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/27904713/farnesoid-x-receptor-ligand-cdca-suppresses-human-prostate-cancer-cells-growth-by-inhibiting-lipid-metabolism-via-targeting-sterol-response-element-binding-protein-1
#5
Nian Liu, Jun Zhao, Jinguo Wang, Haolin Teng, Yaowen Fu, Hang Yuan
AIM: A wealth of studies have demonstrated that abnormal cellular lipid metabolism plays an important role in prostate cancer (PCa) development. Therefore, manipulating lipid metabolism is a potential PCa therapy strategy. In this study, our goal is to investigate the role of farnesoid X receptor (FXR) in regulating the proliferation and lipid metabolism of human PCa cells following its ligand chenodexycholic acid (CDCA) treatment. METHODS: Oil Red O was used to stain lipid contents in PCa cells, and siRNA knockdown was performed to deplete FXR expression...
2016: American Journal of Translational Research
https://www.readbyqxmd.com/read/27903296/factors-affecting-long-term-efficacy-of-t-regulatory-cell-based-therapy-in-type-1-diabetes
#6
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/27902479/identification-of-a-novel-polo-like-kinase-1-inhibitor-that-specifically-blocks-the-functions-of-polo-box-domain
#7
Yunyu Chen, Jing Zhang, Dongsheng Li, Jiandong Jiang, Yanchang Wang, Shuyi Si
Polo-like kinase 1 (Plk1) is a promising target for cancer therapy due to its essential role in cell division. In addition to a highly conserved kinase domain, Plk1 also contains a Polo-Box domain (PBD), which is essential for Plk1's subcellular localization and mitotic functions. We adopted a fluorescence polarization assay and identified a new Plk1 PBD inhibitor T521 from a small-molecule compound library. T521 specifically inhibits the PBD of Plk1, but not those of Plk2-3. T521 exhibits covalent binding to some lysine residues of Plk1 PBD, which causes significant changes in the secondary structure of Plk1 PBD...
November 25, 2016: Oncotarget
https://www.readbyqxmd.com/read/27899359/how-i-treat-atypical-chronic-myeloid-leukemia
#8
Jason Gotlib
Atypical chronic myeloid leukemia, BCR-ABL1-negative (aCML) is a rare myelodysplastic syndrome/myeloproliferative neoplasm for which no current standard of care exists. The challenges of atypical CML relate to its heterogeneous clinical and genetic features, high rate of transformation to acute myeloid leukemia, and historically poor survival. Therefore, allogeneic hematopoietic stem cell transplantation should always be an initial consideration for eligible patients with a suitable donor. Non-transplant approaches for treating aCML have otherwise largely relied on adopting treatment strategies used for MDS and MPN...
November 29, 2016: Blood
https://www.readbyqxmd.com/read/27897332/recent-advances-in-t-cell-immunotherapy-for-haematological-malignancies
#9
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
#10
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
#11
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
#12
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
#13
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
#14
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
#15
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/27888673/clinical-correlates-of-pp65-antigenemia-monitoring-in-the-first-months-of-post-kidney-transplant-in-patients-undergoing-universal-prophylaxis-or-preemptive-therapy
#16
Fabiana Rabe Carvalho, Rachel Ingrid Juliboni Cosendey, Cintia Fernandes Souza, Thalia Medeiros, Paulo Alexandre Menezes, Andrea Alice Silva, Jorge Reis Almeida, Jocemir Ronaldo Lugon
INTRODUCTION: Human cytomegalovirus (HCMV) is a major cause of morbidity in kidney transplant patients. OBJECTIVES: We aimed to study viral replication and serological response in the first months post kidney transplant in patients undergoing universal prophylaxis or preemptive therapy and correlate the findings with the clinical course of HCMV infection. PATIENTS AND METHODS: Independent from the clinical strategy adopted for managing HCMV infection, prophylaxis versus preemptive therapy, the pp65 antigenemia assay and serological response were assessed on the day of transplantation, and then weekly during the first three months of post-transplant...
November 23, 2016: Brazilian Journal of Infectious Diseases
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
#17
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
#18
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
#19
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/27881128/effect-of-intensive-insulin-treatment-on-plasma-levels-of-lipoprotein-associated-phospholipase-a2-and-secretory-phospholipase-a2-in-patients-with-newly-diagnosed-type-2-diabetes
#20
Xiu-Hong Lin, Ming-Tong Xu, Jv-Ying Tang, Li-Fang Mai, Xiao-Yi Wang, Meng Ren, Li Yan
BACKGROUND: China has the highest absolute disease burden of diabetes worldwide. For diabetic patients, diabetes-related vascular complications are major causes of morbidity and mortality. The roles of lipoprotein-associated phospholipase A2 (Lp-PLA2) and secretory phospholipase A2 (sPLA2) as inflammatory markers have been recently evaluated in the pathogenesis of both diabetes and atherosclerosis. We aimed to determine the mechanism through which patients with newly diagnosed type 2 diabetes gain long-term vascular benefit from intensive insulin therapy by evaluating the change in Lp-PLA2 and sPLA2 levels after early intensive insulin treatment and its relevance with insulin resistance and pancreatic β-cell function...
November 23, 2016: Lipids in Health and Disease
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