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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
#1
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
#2
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
#3
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
#4
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
#5
Rutger A Middelburg, Hans Vrielink, Leendert Porcelijn
BACKGROUND: Fetal/Neonatal alloimmune 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
#6
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
#7
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...
October 27, 2016: Diabetologia
https://www.readbyqxmd.com/read/27671676/modulation-of-immune-checkpoints-and-graft-versus-leukemia-in-allogeneic-transplants-by-antagonizing-vasoactive-intestinal-peptide-signaling
#8
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
#9
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
#10
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
#11
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
https://www.readbyqxmd.com/read/27605858/direct-antiglobulin-test-positivity-in-multi-transfused-thalassemics
#12
Ashish Jain, Ajju Agnihotri, Neelam Marwaha, Ratti Ram Sharma
INTRODUCTION: Red cell allo- and auto-immunization is a well recognized problem in multi-transfused thalassemic patients. We conducted this study on 301 multi-transfused thalassemic patients under the Thalassemia Transfusion Programme of Advanced Pediatric Centre of PGIMER. AIMS AND OBJECTIVES: The study was designed to determine the frequency of alloimmunization and autoimmunization in multi-transfused thalassemic patients and to establish the specificity of alloantibody to red cell antigens, if alloimmunization is detected...
July 2016: Asian Journal of Transfusion Science
https://www.readbyqxmd.com/read/27592154/-platelet-transfusion-role-in-neonatal-immune-thrombocytopenia
#13
R Petermann
Neonatal immune thrombocytopenia represent less than 5% of cases of early thrombocytopenia (early-onset<72hours post-delivery). As in adults, thrombocytopenia in neonates is defined as a platelet count less than 150G/L. They are either auto- or allo-immune. Thrombocytopenia resulting from transplacental passage of maternal antibodies directed to platelet membrane glycoproteins can be severe. The major complication of severe thrombocytopenia is bleeding and particularly intra-cranial haemorrhage and neurologic sequelea following...
August 31, 2016: Transfusion Clinique et Biologique: Journal de la Société Française de Transfusion Sanguine
https://www.readbyqxmd.com/read/27559102/mesenchymal-stem-cells-yield-transient-improvements-in-motor-function-in-an-infant-rhesus-macaque-with-severe-early-onset-krabbe-disease
#14
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...
August 24, 2016: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/27507878/pretransplantation-anti-ccr4-antibody-mogamulizumab-against-adult-t-cell-leukemia-lymphoma-is-associated-with-significantly-increased-risks-of-severe-and-corticosteroid-refractory-graft-versus-host-disease-nonrelapse-mortality-and-overall-mortality
#15
Shigeo Fuji, Yoshitaka Inoue, Atae Utsunomiya, Yukiyoshi Moriuchi, Kaoru Uchimaru, Ilseung Choi, Eiichi Otsuka, Hideho Henzan, Koji Kato, Takeaki Tomoyose, Hisashi Yamamoto, Saiko Kurosawa, Ken-Ichi Matsuoka, Takuhiro Yamaguchi, Takahiro Fukuda
PURPOSE: Allogeneic hematopoietic stem-cell transplantation (allo-HSCT) is one important treatment option for patients with aggressive adult T-cell leukemia/lymphoma (ATLL). Mogamulizumab (anti-CCR4 monoclonal antibody; Mog) was recently approved as a treatment for ATLL in Japan. Major concerns exist about the possible adverse effects of pretransplantation Mog because Mog depletes regulatory T cells for several months. We assessed the impact of pretransplantation Mog on clinical outcomes after allo-HSCT...
October 1, 2016: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/27495766/non-hla-antibodies-may-accelerate-immune-responses-after-intestinal-and-multivisceral-transplantation
#16
Undine A Gerlach, Nils Lachmann, Giuseppina Ranucci, Birgit Sawitzki, Constanze Schoenemann, Johann Pratschke, Duska Dragun, Andreas Pascher
BACKGROUND: Non-HLA-allo- and autoantibodies are involved in allograft rejection in kidney and heart transplantation. Their role in intestinal transplantation has not yet been described. We examined the development of anti-Angiotensin II type I receptor antibodies (anti-AT1R) and anti-Endothelin-Type A receptor antibodies (anti-ETAR) associated with the clinical course and histopathological findings of ITX-recipients. METHODS: 37 patients underwent intestinal or multivisceral transplantation...
August 5, 2016: Transplantation
https://www.readbyqxmd.com/read/27472094/costimulation-blockade-in-kidney-transplantation-an-update
#17
Paolo Malvezzi, Thomas Jouve, Lionel Rostaing
In the setting of solid-organ transplantation, calcineurin inhibitor (CNI)-based therapy remains the cornerstone of immunosuppression. However, long-term use of CNIs is associated with some degree of nephrotoxicity. This has led to exploring the blockade of some costimulation pathways as an efficient immunosuppressive tool instead of using CNIs. The only agent already in clinical use and approved by the health authorities for kidney transplant patients is belatacept (Nulojix), a fusion protein that interferes with cytotoxic T lymphocyte-associated protein 4...
November 2016: Transplantation
https://www.readbyqxmd.com/read/27459701/a-review-of-radiation-induced-coagulopathy-and-new-findings-to-support-potential-prevention-strategies-and-treatments
#18
Ann R Kennedy, Amit Maity, Jenine K Sanzari
Results from our recent studies have led to the novel hypothesis that radiation-induced coagulopathy (RIC) and associated hemorrhage occurring as part of the acute radiation syndrome (ARS) is a major cause of death resulting from radiation exposure in large mammals, including humans. This article contains information related to RIC, as well as potential strategies for the prevention and treatment of RIC. In addition, new findings are reported here on the occurrence of RIC biomarkers in humans exposed to radiation...
August 2016: Radiation Research
https://www.readbyqxmd.com/read/27395083/clinical-value-of-non-hla-antibodies-in-kidney-transplantation-still-an-enigma
#19
REVIEW
Laura A Michielsen, Arjan D van Zuilen, Merle M Krebber, Marianne C Verhaar, Henny G Otten
HLA antibodies play a major role in the recipient's immune response against the renal allograft and are an established risk factor for antibody-mediated rejection and subsequent impaired graft survival. Evidence originating from HLA-identical donor-recipient pairs indicates that non-HLA antibodies may play a role as well. Numerous non-HLA antibodies have been identified in renal organ transplantation, directed against a heterogeneous subset of both allo- and autoantigens including MHC Class-I-related chain A (MICA) and Angiotensin II type 1 receptor (AT1R)...
October 2016: Transplantation Reviews
https://www.readbyqxmd.com/read/27362307/preemptive-cd20-b-cell-depletion-attenuates-cardiac-allograft-vasculopathy-in-cd154-treated-monkeys
#20
Agnes M Azimzadeh, Tianshu Zhang, Guosheng Wu, Shahrooz S Kelishadi, Tiffany Stoddard, Natalie OʼNeill, Bao-Ngoc Nguyen, Emily Welty, Christopher Avon, Mitch Higuchi, Stuart L Mitchell, Alena Hershfeld, Xiang-Fei Cheng, Anthony Kronfli, Elana Rybak, Lars Burdorf, Richard N Pierson
BACKGROUND: Anti-CD154 monotherapy is associated with antidonor allo-antibody (Ab) elaboration, cardiac allograft vasculopathy (CAV), and allograft failure in preclinical primate cell and organ transplant models. In the context of calcineurin inhibitors (CNI), these pathogenic phenomena are delayed by preemptive "induction" B cell depletion. METHODS: αCD154 (IDEC-131)-treated cynomolgus monkey heart allograft recipients were given peritransplant rituximab (αCD20) alone or with rabbit antihuman thymocyte globulin...
June 29, 2016: Transplantation
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