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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
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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...
November 28, 2016: 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
#11
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
#12
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
#13
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
#14
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...
October 31, 2016: European Journal of Haematology
https://www.readbyqxmd.com/read/27790618/designer-leptin-receptor-antagonist-allo-aca-inhibits-vegf-effects-in-ophthalmic-neoangiogenesis-models
#15
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
#16
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
https://www.readbyqxmd.com/read/27671676/modulation-of-immune-checkpoints-and-graft-versus-leukemia-in-allogeneic-transplants-by-antagonizing-vasoactive-intestinal-peptide-signaling
#17
Jian-Ming Li, Christopher T Petersen, Jing-Xia Li, Reema Panjwani, Daniel J Chandra, Cynthia R Giver, Bruce R Blazar, Edmund K Waller
The goal of allogeneic bone marrow transplantation (allo-BMT) is elimination of leukemia cells through the graft-versus-leukemia (GvL) activity of donor cells, while limiting graft-versus-host disease (GvHD). Immune checkpoint pathways regulate GvL and GvHD activities, but blocking antibodies or genetic inactivation of these pathways can cause lethal GVHD. Vasoactive intestinal peptide (VIP) is an immunosuppressive neuropeptide that regulates coinhibitory pathways; its role in allo-BMT has not been studied...
December 1, 2016: Cancer Research
https://www.readbyqxmd.com/read/27664133/targeting-immune-checkpoints-in-hematologic-malignancies
#18
REVIEW
Gheath Alatrash, Naval Daver, Elizabeth A Mittendorf
The use of antibodies that target immune checkpoint molecules on the surface of T-lymphocytes and/or tumor cells has revolutionized our approach to cancer therapy. Cytotoxic-T-lymphocyte antigen (CTLA-4) and programmed cell death protein 1 (PD-1) are the two most commonly targeted immune checkpoint molecules. Although the role of antibodies that target CTLA-4 and PD-1 has been established in solid tumor malignancies and Food and Drug Administration approved for melanoma and non-small cell lung cancer, there remains a desperate need to incorporate immune checkpoint inhibition in hematologic malignancies...
October 2016: Pharmacological Reviews
https://www.readbyqxmd.com/read/27648075/allogeneic-mesenchymal-stem-cell-treatment-induces-specific-alloantibodies-in-horses
#19
Sean D Owens, Amir Kol, Naomi J Walker, Dori L Borjesson
Background. It is unknown whether horses that receive allogeneic mesenchymal stem cells (MSCs) injections develop specific humoral immune response. Our goal was to develop and validate a flow cytometric MSC crossmatch procedure and to determine if horses that received allogeneic MSCs in a clinical setting developed measurable antibodies following MSC administration. Methods. Serum was collected from a total of 19 horses enrolled in 3 different research projects. Horses in the 3 studies all received unmatched allogeneic MSCs...
2016: Stem Cells International
https://www.readbyqxmd.com/read/27613101/inhibition-of-b-cell-activation-and-antibody-production-by-triggering-inhibitory-signals-via-the-pd-1-pd-ligand-pathway
#20
Anna Buermann, Dorothee Römermann, Wiebke Baars, Joachim Hundrieser, Jürgen Klempnauer, Reinhard Schwinzer
BACKGROUND: The development of donor-reactive antibodies is regarded to be an important barrier limiting long-term outcome of allo- and xenografts. We asked whether enhanced signaling via the co-inhibitory receptor programmed cell death-1 (PD-1; CD279) can downregulate human B-cell activation. METHODS: Proliferation of human purified CD19(+) B cells was induced by in vitro stimulation with CpG oligodeoxynucleotides (CpG-B). To induce antibody production, peripheral blood mononuclear cells were co-cultured with the porcine B-cell line L23...
September 2016: Xenotransplantation
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