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allogeneic immune therapy

Y Lv, X Pang, P-Y Jia, D-L Jia
OBJECTIVE: Indoleamine 2, 3-dioxygenase (IDO) can inhibit rejection of graft via inducing T cell apoptosis. CD40L monoclonal antibody (mAb) inhibits T cell activation. However, the effects of the combination of infusion of dendritic cell (DC) from IDO over-expressed donor mice and CD40L mAb on the treatment of graft rejection after heart transplantation have not been reported. MATERIALS AND METHODS: Allogeneic heart transplantation mouse model was established. Recipient mice were divided into three groups, including control group, IDO group (in which DC donors received adenoviral vector of IDO) and combined therapy group (which received both IDO over-expressed DC infusion and CD40L mAb injection post transplantation)...
November 2018: European Review for Medical and Pharmacological Sciences
Yusuke Narita, Tatsuki Uchiyama, Chisaki Mizumoto, Tomoharu Takeoka, Kenjiro Tomo, Masaaki Tsuji, Tatsuharu Ohno
A 44-year-old woman in the first remission phase of mixed-phenotype acute leukemia (T-lymphoid and myeloid lineages) suddenly exhibited thrombocytopenia (1.1×104 /µl) with generalized petechiae approximately 150 days after bone marrow transplantation (BMT) from a one-locus (HLA-B) mismatched unrelated donor. Until then, the donor bone marrow had smoothly engrafted, and the platelet count had promptly normalized. Despite extensively searching for the triggering agent such as GVHD, graft failure, relapsed leukemia, or adverse drug effects, it could not be determined...
2018: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
Rieneke van de Ven, Traci L Hilton, Hong-Ming Hu, Christopher J Dubay, Daniel Haley, Christopher Paustian, Sachin Puri, Walter J Urba, Brendan D Curti, Sandra Aung, Bernard A Fox
The immune system plays an essential role in eradicating cancer in concert with various treatment modalities. In the absence of autologous tumor material, no standardized method exists to assess T cell responses against the many antigens that may serve as cancer rejection antigens. Thus, development of methods to screen for therapy-induced anti-tumor responses is a high priority that could help tailor therapy. Here we tested whether a tumor-derived antigen source called DRibbles®, which contain a pool of defective ribosomal products (DRiPs), long-lived and short-lived proteins (SLiPs) and danger-associated molecular patterns (DAMPs), can be used to identify tumor-associated antigen (TAA)-specific responses in patients before or after immunotherapy treatment...
2018: Oncoimmunology
Reena Kumari, Senthilnathan Palaniyandi, Gerhard Carl Hildebrandt
Hematopoietic cell transplantation is an intensive therapy used to treat high-risk hematological malignant disorders and other life-threatening hematological and genetic diseases. Graft-versus-host disease (GVHD) presents a barrier to its wider application. A conditioning regimen and medications given to patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HCT) are capable of disturbing the homeostatic crosstalk between the microbiome and the host immune system and of leading to dysbiosis...
December 7, 2018: Digestive Diseases and Sciences
Jakub Suchánek, Klara Zoe Browne, Sherine Adel Nasry, Tereza Suchánková Kleplová, Nela Pilbauerová, Jan Schmidt, Tomáš Soukup
Recently, human natal dental pulp stem cells (hNDP-SCs) have been characterized in vitro and it has been shown that they satisfy criteria defining human mesenchymal stromal cells (MSCs), as proposed by the International Society for Cellular Therapy. However, these results were reached in the presence of xenogeneic expansion medium, which has the potential to alter the cells' functional capacity. To determine the validity of the previously reported hNDP-SCs characteristics for human cell therapy, we have cultured hNDP-SCs in allogeneic expansion medium...
September 2018: Brazilian Dental Journal
Kerstin Rauwolf, Heidi Herbrüggen, Stefan Zöllner, Heike Thorer, Olga Makarova, Thomas Kaiser, Aleksandra Pettke, Claudia Rossig, Birgit Burkhardt, Andreas H Groll
Chronic hepatitis C virus (HCV) infection carries increased risks for morbidity and mortality in patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT) but has become curable through the advent of directly acting antiviral compounds. Current guidelines of the American Society for Blood and Marrow Transplantation (ASBMT) recommend that HCV-infected HSCT candidates preferably start and complete therapy prior to transplant. However, this is often not feasible due to time constraints or treatment limiting comorbidities, conditions and treatments...
December 5, 2018: Journal of Viral Hepatitis
Paul Lohan, Nick Murphy, Oliver Treacy, Kevin Lynch, Maurice Morcos, Bingling Chen, Aideen E Ryan, Matthew D Griffin, Thomas Ritter
High-risk cornea transplant recipients represent a patient population with significant un-met medical need for more effective therapies to prevent immunological graft rejection due to heightened anti-donor immune response. In this study, a rat model of pre-existing anti-donor immunity was developed in which corneal allografts were rejected earlier than in non-pre-sensitized recipients. In this model, third-party (non-donor, non-recipient strain) allogeneic mesenchymal stromal cells (allo-MSC) were administered intravenously 7 and 1 days prior to transplantation...
2018: Frontiers in Immunology
Fatemeh Rezaei, Seyed Mohammad Moazzeni
Objective: Mesenchymal stem cells (MSCs), due to their immunomodulatory functions, are an ideal candidate for the treatment of immune-related diseases. Recurrent spontaneous abortion (RSA) is one of the most common complications of pregnancy which in many cases is related to the immune system disorders. Our previous study has shown that the abortion rate was decreased following the syngeneic MSCs therapy in abortion-prone mice. In this study, the therapeutic effect of syngeneic, allogeneic, and xenogeneic MSCs was compared in a mouse model of RSA...
April 2019: Cell Journal
Weihong Li, Lihong Geng, Xiru Liu, Wenwu Gui, Hongbo Qi
Recurrent spontaneous abortion (RSA) is associated with abnormal maternal tolerance to the semi-allogenic fetus, wherein the Th17/Treg axis plays a crucial role. Adiponectin (APN) is an adipocytokine that is shown to be a novel negative T-cell regulator and induce immune tolerance. The CBA/J × DBA/2 mating was used as an abortion-prone model to investigate whether the addition of recombinant adiponectin (rAPN) improves the pregnancy outcome. rAPN therapy reduced the abortion rate in abortion-prone model...
November 28, 2018: Biology of Reproduction
Saidulu Mattapally, Kevin M Pawlik, Vladimir G Fast, Esther Zumaquero, Frances E Lund, Troy D Randall, Tim M Townes, Jianyi Zhang
Background We aim to generate a line of "universal donor" human induced pluripotent stem cells (hi PSC s) that are nonimmunogenic and, therefore, can be used to derive cell products suitable for allogeneic transplantation. Methods and Results hi PSC s carrying knockout mutations for 2 key components (β2 microglobulin and class II major histocompatibility class transactivator) of major histocompatibility complexes I and II (ie, human leukocyte antigen [HLA] I/ II knockout hi PSC s) were generated using the Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/CRISPR associated protein 9 (Cas9) gene-editing system and differentiated into cardiomyocytes...
December 4, 2018: Journal of the American Heart Association
Daniel Y Lee, Kwang Suk Lim, Gabriel M Valencia, Minjin Jung, David A Bull, Young-Wook Won
Conventional combinatorial anticancer therapy has shown promising outcomes; still, a significant interest in developing new methods to reinforce and possibly merge chemotherapy and immunotherapy persists. Here, a new one-step method that immediately modifies immune cells into a targeted form of chemoimmunotherapy through spontaneous and rapid incorporation of hydrophobized antibody-drug conjugates (ADCs) on the surface of immune cells is presented. Therapeutic objectives of this approach include targeted delivery of a potent chemotherapeutic agent to avoid adverse effects, enhancing the mobilization of infused immune cells toward tumor sites, and preserving the intense cytotoxic activities of immune cells against tumor cells...
November 2018: Advanced Science (Weinheim, Baden-Wurttemberg, Germany)
Michael Skoumal, Kyle B Woodward, Hong Zhao, Feng Wang, Esma S Yolcu, Ryan M Pearson, Kevin R Hughes, Andrés J García, Lonnie D Shea, Haval Shirwan
Intraportal allogeneic islet transplantation has been demonstrated as a potential therapy for type 1 diabetes (T1D). The placement of islets into the liver and chronic immunosuppression to control rejection are two major limitations of islet transplantation. We hypothesize that localized immunomodulation with a novel form of FasL chimeric with streptavidin, SA-FasL, can provide protection and long-term function of islets at an extrahepatic site in the absence of chronic immunosuppression. Allogeneic islets modified with biotin and engineered to transiently display SA-FasL on their surface showed sustained survival following transplantation on microporous scaffolds into the peritoneal fat in combination with a short course (15 days) of rapamycin treatment...
November 13, 2018: Biomaterials
Masaaki Hotta, Hideaki Yoshimura, Atsushi Satake, Yukie Tsubokura, Tomoki Ito, Shosaku Nomura
Regulatory T cells (Tregs) attenuate excessive immune responses, making their expansion beneficial in immune-mediated diseases, including allogeneic bone marrow transplantation-associated graft-versus-host disease (GVHD). In addition to interleukin-2, Tregs require T cell receptor and costimulatory signals from antigen-presenting cells, such as dendritic cells (DCs), for their optimal proliferation. Granulocyte-macrophage colony stimulating factor (GM-CSF) increases DC number and may promote DC-dependent Treg proliferation...
November 20, 2018: European Journal of Immunology
Marek Ussowicz, Elżbieta Wawrzyniak-Dzierżek, Monika Mielcarek-Siedziuk, Małgorzata Salamonowicz, Jowita Frączkiewicz, Blanka Rybka, Renata Ryczan-Krawczyk, Krzysztof Kałwak
Ataxia-telangiectasia (A-T) syndrome is an autosomal recessive chromosomal breakage syndrome caused by mutation of the ataxia-telangiectasia mutated gene manifested by progressive neurodegeneration, telangiectasias of sclera and skin, immune deficiency with sinopulmonary infections, and increased incidence of lymphoid malignancies and solid tumors. Three children with A-T underwent allogeneic stem cell transplantation (SCT) using protocols for Fanconi anemia. All 3 patients were engrafted with a mixed donor-recipient chimerism, but the full donor engraftment was observed in the T lymphocyte compartment...
November 2018: Biology of Blood and Marrow Transplantation
Farhad Ravandi
The introduction of agents targeted at specific molecular events is changing the treatment paradigms in a number of malignancies. Historically, we have relied entirely on DNA-interactive, cytotoxic drugs for treating patients with leukemia. Increased understanding of the leukemic cell biology and pathogenesis, and the ways they evade the immune surveillance mechanisms, will likely lead to the development of more effective agents, and regimens less reliant on chemotherapy, able to achieve deep levels of disease eradication...
November 15, 2018: Blood
Liat Shargian-Alon, Pia Raanani, Uri Rozovski, Tali Siegal, Shlomit Yust-Katz, Moshe Yeshurun
Neurologic complications of allogeneic hematopoietic cell transplantation (allo-HCT) include infections, cerebrovascular events, therapy-induced neurotoxicity, recurrent malignancies, and neurologic manifestations of graft-versus-host disease (GVHD). Anti-glutamic acid decarboxylase (GAD) antibody-associated cerebellar ataxia is a well-established disorder of autoimmune origin, but there are no reports in the literature of its occurrence following allo-HCT. We describe a middle-aged woman with chronic GVHD after allo-HCT who presented with a rapidly progressive cerebellar syndrome...
November 15, 2018: Acta Haematologica
Macartney Welborn, Madeleine Duvic
Cutaneous T-cell lymphomas (CTCLs) are a group of non-Hodgkin's lymphomas that present in the skin. In early-stage disease, the course is generally chronic and indolent; however, in advanced stages of disease, therapies rarely provide long-lasting responses, and the only potential curative therapy is allogeneic hematopoietic stem-cell transplantation. This has led to the search for novel targeted therapies to better treat more advanced stages of CTCLs that cannot be controlled by typical treatment regimens...
November 15, 2018: American Journal of Clinical Dermatology
Nadja Hilger, Claudia Mueller, Lilly Stahl, Anne M Mueller, Bianca Zoennchen, Sarah Dluczek, Christoph Halbich, Claudia Wickenhauser, Dennis Gerloff, Alexander A Wurm, Gerhard Behre, Anna Kretschmer, Stephan Fricke
Despite the constant development of innovative therapeutic options for hematological malignancies, the gold-standard therapy regimen for curative treatment often includes allogeneic hematopoietic stem cell transplantation (HSCT). The graft-vs.-leukemia effect (GVL) is one of the main therapeutic goals that arises from HSCT. On the other hand, graft-vs.-host disease (GVHD) is still one of the main and most serious complications following allogeneic HSCT. In acute myeloid leukemia (AML), HSCT together with high-dose chemotherapy is used as a treatment option...
2018: Frontiers in Immunology
Maria J Sebastião, Ramón Menta, Margarida Serra, Itziar Palacios, Paula M Alves, Belén Sanchez, Olga DelaRosa, Wilfried Dalemans, Eleuterio Lombardo, Patrícia Gomes-Alves
Transplantation of allogeneic human cardiac/stem progenitor cells (hCSCs) is currently being tested in several phase I/II clinical trials as a novel and promising therapy for restoration of myocardial tissue function in acute myocardial infarction (AMI) patients. Previous findings demonstrate that these cells have an immune suppressive profile interacting with different populations from the immune system, resulting in overall attenuation of myocardial inflammation. However, transplanted hCSCs are still recognized and cleared from the injured site, impairing long retention times in the tissue that could translate into a higher clinical benefit...
October 25, 2018: Stem Cell Research & Therapy
Holger Budde, Susanne Papert, Holger M Reichardt, Hubertus Jarry, Joachim Riggert, Tobias J Legler
BACKGROUND AND OBJECTIVE: Extracorporeal photopheresis (ECP) is an important immune tolerance inducing therapy for graft-versus-host disease (GvHD). However, a sufficient number of ECP cycles cannot be performed in patients with severe GvHD and contraindications for apheresis. Allogeneic sources of leucocytes for use as ECP treatment would be of great benefit. Therefore, this study aimed to test the therapeutic potential of novel sources of leucocytes for ECP. MATERIALS AND METHODS: Graft-versus-host disease mice were treated with ECP using therapeutic cells from different allogeneic sources...
October 23, 2018: Vox Sanguinis
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