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https://www.readbyqxmd.com/read/28331127/the-impact-of-a-humanized-ccr4-antibody-mogamulizumab-on-patients-with-aggressive-type-adult-t-cell-leukemia-lymphoma-treated-with-allogeneic-hematopoietic-stem-cell-transplantation
#1
Noriaki Kawano, Takuro Kuriyama, Shuro Yoshida, Sayaka Kawano, Yoshihisa Yamano, Kousuke Marutsuka, Seiichirou Minato, Kiyoshi Yamashita, Hidenobu Ochiai, Kazuya Shimoda, Fumihiko Ishikawa, Ikuo Kikuchi
Although a humanized CCR4 antibody (mogamulizumab) was reported to be effective for refractory adult T-cell leukemia-lymphoma (ATL), several reports regarding the use of mogamulizumab before allo-hematopoietic stem cell transplantation (HSCT) strongly indicated a high incidence of severe acute graft-versus-host-disease (GVHD) and treatment-related mortality (TRM). We retrospectively analyzed nine aggressive-type ATL patients who underwent allo-HSCT at a single institution in Miyazaki from 2006.1.1 to 2015.7...
2017: Journal of Clinical and Experimental Hematopathology: JCEH
https://www.readbyqxmd.com/read/28303517/vascular-and-perivascular-niches-but-not-the-osteoblastic-niche-are-numerically-restored-following-allogeneic-hematopoietic-stem-cell-transplantation-in-patients-with-aplastic-anemia
#2
Liangliang Wu, Wenjian Mo, Yuping Zhang, Ming Zhou, Yumiao Li, Ruiqing Zhou, Shiling Xu, Shiyi Pan, Hui Deng, Ping Mao, Shunqing Wang
Bone marrow (BM) niches, including the osteoblastic, vascular, and perivascular niches, are numerically impaired in patients with aplastic anemia (AA). It remains unclear whether these niches are numerically restored in AA patients after allogenic hematopoietic stem cell transplantation (allo-HSCT). To investigate changes in BM niches, we monitored 52 patients with AA who had undergone allo-HSCT and performed immunohistochemical studies of BM niches using antibodies against CD34, CD146, and osteopontin. After allo-HSCT, patients with AA exhibited a remarkable increase in the number of cellular elements in the BM niches, including the vascular and perivascular cells...
March 16, 2017: International Journal of Hematology
https://www.readbyqxmd.com/read/28270452/efficacy-and-tolerability-of-nivolumab-after-allogeneic-transplantation-for-relapsed-hodgkin-s-lymphoma
#3
Charles Herbaux, Jordan Gauthier, Pauline Brice, Elodie Drumez, Loic Ysebaert, Hélène Doyen, Luc Fornecker, Krimo Bouabdallah, Guillaume Manson, Hervé Ghesquières, Reza Tabrizi, Eric Hermet, Julien Lazarovici, Anne Thiebaut-Bertrand, Adrien Chauchet, Hélène Demarquette, Eileen Boyle, Roch Houot, Ibrahim Yakoub-Agha, Franck Morschhauser
Allogeneic hematopoietic cell transplantation (allo-HCT) is indicated for patients with relapsed and refractory Hodgkin lymphoma (HL). While long-term disease control can be achieved, relapse remains frequent. The programmed death 1 (PD-1) blocking antibody nivolumab has shown substantial therapeutic activity and an acceptable safety profile in relapsed and refractory HL who did not receive allo-HCT. However, PD-1-blocking strategy can increase the risk of Graft Versus Host Disease (GVHD) in murine models. We retrospectively assessed the efficacy and toxicity of nivolumab as a single agent in 20 HL patients relapsing after allo-HCT...
March 7, 2017: Blood
https://www.readbyqxmd.com/read/28255564/endothelial-cells-in-antibody-mediated-rejection-of-kidney-transplantation-pathogenesis-mechanisms-and-therapeutic-implications
#4
REVIEW
Shuo Wang, Chao Zhang, Jina Wang, Cheng Yang, Ming Xu, Ruiming Rong, Tongyu Zhu, Dong Zhu
Antibody-mediated rejection (AMR) has been identified as a main obstacle for stable immune tolerance and long survival of kidney allografts. In spite of new insights into the underlying mechanisms of AMR, accurate diagnosis and efficient treatment are still challenges in clinical practice. Endothelium is the first barrier between recipients' immune systems and grafts in vascularized organ transplants. Considering that endothelial cells express a number of antigens that can be attacked by various allo- and autoantibodies, endothelial cells act as main targets for the recipients' humoral immune responses...
2017: Journal of Immunology Research
https://www.readbyqxmd.com/read/28170189/mesenchymal-stem-cells-yield-transient-improvements-in-motor-function-in-an-infant-rhesus-macaque-with-severe-early-onset-krabbe-disease
#5
Irina A Isakova, Kate C Baker, Jason Dufour, Donald G Phinney
Krabbe disease, or globoid cell leukodystrophy, is a rare disorder caused by deficient galactosylceramidase activity and loss of myelin-forming oligodendrocytes, resulting in progressive demyelination and severely impaired motor function. Disease symptoms in humans appear within 3-6 months of age (early infantile) and manifest as marked irritability, spasticity, and seizures. The disease is often fatal by the second year of life, with few effective treatment options. Herein we evaluated the therapeutic potential of mesenchymal stem cells (MSCs) administered intracranially to a 1-month-old rhesus macaque diagnosed with severe early-onset Krabbe disease that displayed neurologic and behavioral symptoms similar to those of human patients...
January 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28167271/late-onset-cytopenias-following-haematopoietic-stem-cell-transplant-associated-with-viral-infection-and-cell-specific-antibodies
#6
Geoff Lucas, Steven Culliford, Nina Bendukidze, Julia Dahlstrom, Victoria Grandage, Ben Carpenter, Rachael Hough
This report describes a patient who received an allogeneic haematopoietic stem cell transplant and who, following a viral infection, developed late onset cytopenias associated with antibodies against red cells, platelets and granulocytes. Investigation of these cytopenias revealed the presence of lineage specific auto- and allo-antibodies, which were not present in either the donor or in the recipient prior to the viral infection. This case provides further evidence for the concept that viral challenges following HSCT can result in the production of cell specific antibodies that can have significant implications for patient management...
February 3, 2017: Transplant Immunology
https://www.readbyqxmd.com/read/28117787/use-of-a-monocyte-monolayer-assay-to-evaluate-fc%C3%AE-receptor-mediated-phagocytosis
#7
Tik Nga Tong, Donald R Branch
Although originally developed for predicting transfusion outcomes of serologically incompatible blood, the monocyte monolayer assay (MMA) is a highly versatile in vitro assay that can be modified to examine different aspects of antibody and Fcγ receptor (FcγR)-mediated phagocytosis in both research and clinical settings. The assay utilizes adherent monocytes from peripheral blood mononuclear cells isolated from mammalian whole blood. MMA has been described for use in both human and murine investigations. These monocytes express FcγRs (e...
January 2, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28117403/minimizing-the-risk-of-allo-sensitization-to-optimize-the-benefit-of-allogeneic-cardiac-derived-stem-progenitor-cells
#8
Hocine R Hocine, Hicham E L Costa, Noemie Dam, Jerome Giustiniani, Itziar Palacios, Pascale Loiseau, Armand Benssusan, Luis R Borlado, Dominique Charron, Caroline Suberbielle, Nabila Jabrane-Ferrat, Reem Al-Daccak
Allogeneic human cardiac-derived stem/progenitor cells (hCPC) are currently under clinical investigation for cardiac repair. While cellular immune response against allogeneic hCPC could be part of their beneficial-paracrine effects, their humoral immune response remains largely unexplored. Donor-specific HLA antibodies (DSA-HLA-I/DSA-HLA-II), primary elements of antibody-mediated allograft injury, might present an unidentified risk to allogeneic hCPC therapy. Here we established that the binding strength of anti-HLA monoclonal antibodies delineates hCPC proneness to antibody-mediated injury...
January 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28099485/cell-based-systems-biology-analysis-of-human-as03-adjuvanted-h5n1-avian-influenza-vaccine-responses-a-phase-i-randomized-controlled-trial
#9
Leigh M Howard, Kristen L Hoek, Johannes B Goll, Parimal Samir, Allison Galassie, Tara M Allos, Xinnan Niu, Laura E Gordy, C Buddy Creech, Nripesh Prasad, Travis L Jensen, Heather Hill, Shawn E Levy, Sebastian Joyce, Andrew J Link, Kathryn M Edwards
BACKGROUND: Vaccine development for influenza A/H5N1 is an important public health priority, but H5N1 vaccines are less immunogenic than seasonal influenza vaccines. Adjuvant System 03 (AS03) markedly enhances immune responses to H5N1 vaccine antigens, but the underlying molecular mechanisms are incompletely understood. OBJECTIVE AND METHODS: We compared the safety (primary endpoint), immunogenicity (secondary), gene expression (tertiary) and cytokine responses (exploratory) between AS03-adjuvanted and unadjuvanted inactivated split-virus H5N1 influenza vaccines...
2017: PloS One
https://www.readbyqxmd.com/read/28097534/successful-treatment-with-low-dose-nivolumab-in-refractory-hodgkin-lymphoma-after-allogeneic-stem-cell-transplantation
#10
Makoto Onizuka, Minoru Kojima, Keiko Matsui, Shinichiro Machida, Masako Toyosaki, Yasuyuki Aoyama, Hidetsugu Kawai, Jun Amaki, Ryujiro Hara, Akifumi Ichiki, Yoshiaki Ogawa, Hiroshi Kawada, Naoya Nakamura, Kiyoshi Ando
Previous studies have reported that an antibody that blocks programmed cell death 1 (PD-1) has therapeutic activity in patients with refractory/relapsed Hodgkin lymphoma (HL). However, the safety and efficacy of these agents in the post-allogeneic stem cell transplantation (allo-SCT) setting are not well known. Here, we describe a patient who was diagnosed as classical HL and treated with five regimens of chemotherapies with autologous SCT. Complete remission (CR) was not achieved following this initial treatment, so we performed allo-SCT from an HLA-matched sibling donor...
January 17, 2017: International Journal of Hematology
https://www.readbyqxmd.com/read/28096093/lymphangiogenesis-is-a-feature-of-acute-gvhd-and-vegfr-3-inhibition-protects-against-experimental-gvhd
#11
Sarah Mertlitz, Yu Shi, Martina Kalupa, Carsten Grötzinger, Jörg Mengwasser, Katarina Riesner, Steffen Cordes, Sefer Elezkurtaj, Olaf Penack
Lymph vessels play a crucial role for immune reactions in health and disease. In oncology the inhibition of lymphangiogenesis is an established therapeutic concept to reduce metastatic spreading of tumor cells. During allogeneic tissue transplantation the inhibition of lymphangiogenesis has been successfully used to attenuate graft rejection. Despite its critical importance for tumor growth, allo-immune responses and inflammation, the role of lymphangiogenesis has not been investigated during allogeneic hematopoietic stem cell transplantation (allo-HSCT)...
January 17, 2017: Blood
https://www.readbyqxmd.com/read/28028710/restoring-ovarian-endocrine-function-with-encapsulated-ovarian-allograft-in-immune-competent-mice
#12
Anu David, James Ronald Day, Alexa Leigh Cichon, Adam Lefferts, Marilia Cascalho, Ariella Shikanov
Premature ovarian insufficiency (POI) is a major complication of cytotoxic treatments due to extreme ovarian sensitivity to chemotherapy and radiation. In pediatric cancer patients modern therapy has improved the long-term survival to over 80% in the United States. However, these cancer survivors face long-term health problems related to treatment toxicity. In female cancer survivors POI leads to sterility, along with the consequences of estrogen deficiency such as premature osteopenia, muscle wasting, accelerated cardiovascular diseases and a vast array of other health and developmental problems...
December 27, 2016: Annals of Biomedical Engineering
https://www.readbyqxmd.com/read/27939210/studies-of-innate-immune-systems-against-human-cells
#13
Rieko Sakai, Etsuko Kitano, Akira Maeda, Pei-Chi Lo, Hiroshi Eguchi, Masahito Watanabe, Hiroshi Nagashima, Hiroomi Okuyama, Shuji Miyagawa
BACKGROUND: Pigs are frequently used as animal models for experiments in the surgical field, including allo- and xeno-transplantation. Regeneration studies, including studies dealing with human- and monkey-induced pluripotent stem cells (iPSC), have gradually progressed, with pigs sometimes being used as the scaffold. However, the immunological response of pigs against humans, especially innate immunities, remain unclear. This study reports on a comprehensive study of pig innate immunity against humans...
December 7, 2016: Transplant Immunology
https://www.readbyqxmd.com/read/27896368/targeting-of-the-wt191-138-fragment-to-human-dendritic-cells-improves-leukemia-specific-t-cell-responses-providing-an-alternative-approach-to-wt1-based-vaccination
#14
Nergui Dagvadorj, Anne Deuretzbacher, Daniela Weisenberger, Elke Baumeister, Johannes Trebing, Isabell Lang, Carolin Köchel, Markus Kapp, Kerstin Kapp, Andreas Beilhack, Thomas Hünig, Hermann Einsele, Harald Wajant, Götz Ulrich Grigoleit
Due to its immunogenicity and overexpression concomitant with leukemia progression, Wilms tumor protein 1 (WT1) is of particular interest for immunotherapy of AML relapse after allogeneic hematopoietic stem cell transplantation (allo-HSCT). So far, WT1-specific T-cell responses have mainly been induced by vaccination with peptides presented by certain HLA alleles. However, this approach is still not widely applicable in clinical practice due to common limitations of HLA restriction. Dendritic cell (DC) vaccines electroporated with mRNA encoding full-length protein have also been tested for generating WT1-derived peptides for presentation to T-cells...
March 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/27874054/combinational-immunotherapy-with-allo-dribble-vaccines-and-anti-ox40-co-stimulation-leads-to-generation-of-cross-reactive-effector-t-cells-and-tumor-regression
#15
Guangjie Yu, Yuhuan Li, Zhihua Cui, Nicholas P Morris, Andrew D Weinberg, Bernard A Fox, Walter J Urba, Lixin Wang, Hong-Ming Hu
It is well-known that vaccines comprising of irradiated whole tumor cells or tumor-derived heat shock proteins can generate tumor-specific immune responses. In contrast, we showed recently that vaccines composed of autophagosomes (DRibbles) derived from syngeneic sarcomas could induce cross-reactive T-cell responses and cross-protection against the tumor. This unusual property of DRibbles was related to the selective recruitment of defective ribosomal products (DRiPs) and other short-lived proteins (SLiPs) into autophagosomes via sequestosome (SQSTM1, p62) mediated association of ubiquitinated SLiPs to the autophagy gene product LC3...
November 22, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27868052/friend-or-foe-mogamulizumab-in-allogeneic-hematopoietic-stem-cell-transplantation-for-adult-t-cell-leukemia-lymphoma
#16
REVIEW
Shigeo Fuji, Takero Shindo
Adult T-cell leukemia/lymphoma (ATL/ATLL) is a peripheral T-cell neoplasm associated with human T-lymphotropic virus type-1 (HTLV-1). Even the currently most intensive chemotherapy regimen modified LSG15 (mLSG15, VCAP-AMP-VECP) results in a dismal clinical outcome, with a median overall survival of only around 1 year. Although allogeneic hematopoietic stem cell transplantation (allo-HSCT) may lead to long-term remission in a proportion of patients with aggressive ATL, the clinical outcome in patients with refractory or relapsed ATL is unsatisfactory...
2016: Stem Cell Investigation
https://www.readbyqxmd.com/read/27818660/unraveling-the-role-of-allo-antibodies-and-transplant-injury
#17
REVIEW
Yoshiko Matsuda, Minnie M Sarwal
Alloimmunity driving rejection in the context of solid organ transplantation can be grossly divided into mechanisms predominantly driven by either T cell-mediated rejection (TCMR) and antibody-mediated rejection (ABMR), though the co-existence of both types of rejections can be seen in a variable number of sampled grafts. Acute TCMR can generally be well controlled by the establishment of effective immunosuppression (1, 2). Acute ABMR is a low frequency finding in the current era of blood group and HLA donor/recipient matching and the avoidance of engraftment in the context of high-titer, preformed donor-specific antibodies...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/27797412/prevalence-of-granulocyte-antibodies-in-never-allo-exposed-female-and-male-donors
#18
Rutger A Middelburg, Hans Vrielink, Leendert Porcelijn
BACKGROUND: Foetal/neonatal allo-immune neutropenia (FNAIN) is a serious condition usually resulting from immunisation of the mother to paternally inherited neutrophil antigens of the foetus. Understanding the biology of female immunisation against neutrophils could help predict or prevent FNAIN. OBJECTIVES: To quantify differences in the prevalence of specific and pan-reactive granulocyte antibodies, between allo-exposed and never allo-exposed male and female blood donors...
March 2017: European Journal of Haematology
https://www.readbyqxmd.com/read/27790618/designer-leptin-receptor-antagonist-allo-aca-inhibits-vegf-effects-in-ophthalmic-neoangiogenesis-models
#19
Roberta Coroniti, Rafal Fario, Didier J Nuno, Laszlo Otvos, Laura Scolaro, Eva Surmacz
Experimental and clinical data suggest that pro-angiogenic, pro-inflammatory and mitogenic cytokine leptin can be implicated in ocular neovascularization and other eye pathologies. At least in part, leptin action appears to be mediated through functional interplay with vascular endothelial growth factor (VEGF). VEGF is a potent regulator of neoangiogenesis and vascular leakage with a proven role in conditions such as proliferative diabetic retinopathy, age-related macular degeneration and diabetic macular edema...
2016: Frontiers in Molecular Biosciences
https://www.readbyqxmd.com/read/27787618/immunogenicity-of-human-embryonic-stem-cell-derived-beta-cells
#20
Cornelis R van der Torren, Arnaud Zaldumbide, Gaby Duinkerken, Simone H Brand-Schaaf, Mark Peakman, Geert Stangé, Laura Martinson, Evert Kroon, Eugene P Brandon, Daniel Pipeleers, Bart O Roep
AIMS/HYPOTHESIS: To overcome the donor shortage in the treatment of advanced type 1 diabetes by islet transplantation, human embryonic stem cells (hESCs) show great potential as an unlimited alternative source of beta cells. hESCs may have immune privileged properties and it is important to determine whether these properties are preserved in hESC-derived cells. METHODS: We comprehensively investigated interactions of both innate and adaptive auto- and allo-immunity with hESC-derived pancreatic progenitor cells and hESC-derived endocrine cells, retrieved after in-vivo differentiation in capsules in the subcutis of mice...
January 2017: Diabetologia
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