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Dendritic Cell Therapy

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https://www.readbyqxmd.com/read/29785027/targeting-g-quadruplex-dna-as-cognitive-function-therapy-for-atr-x-syndrome
#1
Norifumi Shioda, Yasushi Yabuki, Kouya Yamaguchi, Misaki Onozato, Yue Li, Kenji Kurosawa, Hideyuki Tanabe, Nobuhiko Okamoto, Takumi Era, Hiroshi Sugiyama, Takahito Wada, Kohji Fukunaga
Alpha-thalassemia X-linked intellectual disability (ATR-X) syndrome is caused by mutations in ATRX, which encodes a chromatin-remodeling protein. Genome-wide analyses in mouse and human cells indicate that ATRX tends to bind to G-rich sequences with a high potential to form G-quadruplexes. Here, we report that Atrx mutation induces aberrant upregulation of Xlr3b expression in the mouse brain, an outcome associated with neuronal pathogenesis displayed by ATR-X model mice. We show that ATRX normally binds to G-quadruplexes in CpG islands of the imprinted Xlr3b gene, regulating its expression by recruiting DNA methyltransferases...
May 21, 2018: Nature Medicine
https://www.readbyqxmd.com/read/29784675/radiation-followed-by-ox40-stimulation-drives-local-and-abscopal-antitumor-effects-in-an-anti-pd1-resistant-lung-tumor-model
#2
Sharareh Niknam, Hampartsoum B Barsoumian, Jonathan E Schoenhals, Heather Jackson, Niranjan Yanamandra, Mauricio S Caetano, Ailin Li, Ahmed I Younes, Alexandra P Cadena, Taylor R Cushman, Joe Y Chang, Quynh Nguyen, Daniel R Gomez, Adi Diab, John V Heymach, Patrick Hwu, Maria Angelica Cortez, James W Welsh
PURPOSE: Radiation is used extensively to treat localized cancer, but improved understanding of its effects on the immune system have increased interest in its potential systemic (abscopal) effects, particularly in combination with checkpoint inhibitors such as anti-PD1. The majority of patients either do not respond or develop resistance to monotherapy over time. Here, we investigated the efficacy of OX40 (CD134) stimulation as an alternative immunotherapeutic approach in combination with radiotherapy (XRT) in a murine model of anti-PD1-resistant lung tumors...
May 21, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29774608/virion-like-membrane-breaking-nanoparticles-with-tumor-activated-cell-and-tissue-dual-penetration-conquer-impermeable-cancer
#3
Xiao Zhang, Xianghui Xu, Yachao Li, Cheng Hu, Zhijun Zhang, Zhongwei Gu
Poor drug penetration into tumor cells and tissues is a worldwide difficulty in cancer therapy. A strategy is developed for virion-like membrane-breaking nanoparticles (MBNs) to smoothly accomplish tumor-activated cell-and-tissue dual-penetration for surmounting impermeable drug-resistant cancer. Tailor-made dendritic arginine-rich peptide prodrugs are designed to mimic viral protein transduction domains and globular protein architectures. Attractively, these protein mimics self-assemble into virion-like nanoparticles in aqueous solution, having highly ordered secondary structure...
May 17, 2018: Advanced Materials
https://www.readbyqxmd.com/read/29774025/co-stimulation-impaired-bone-marrow-derived-dendritic-cells-prevent-dextran-sodium-sulfate-induced-colitis-in-mice
#4
Carl Engman, Yesica Garciafigueroa, Brett Eugene Phillips, Massimo Trucco, Nick Giannoukakis
Dendritic cells (DC) are important in the onset and severity of inflammatory bowel disease (IBD). Tolerogenic DC induce T-cells to become therapeutic Foxp3+ regulatory T-cells (Tregs). We therefore asked if experimental IBD could be prevented by administration of bone marrow-derived DC generated under conventional GM-CSF/IL-4 conditions but in the presence of a mixture of antisense DNA oligonucleotides targeting the primary transcripts of CD40, CD80, and CD86. These cell products (which we call AS-ODN BM-DC) have demonstrated tolerogenic activity in preventing type 1 diabetes and preserving beta cell mass in new-onset type 1 diabetes in the NOD mouse strain, in earlier studies...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29772024/use-of-human-amniotic-epithelial-cells-in-mouse-models-of-bleomycin-induced-lung-fibrosis-a-systematic-review-and-meta-analysis
#5
Fang He, Aiting Zhou, Shuo Feng
BACKGROUND: Idiopathic pulmonary fibrosis (IPF) urgently requires effective treatment. Bleomycin-induced lung injury models are characterized by initial inflammation and secondary fibrosis, consistent with the pathological features of IPF. Human amniotic epithelial cells (hAECs) exhibit good differentiation potential and paracrine activity and are thus ideal for cell-based clinical therapies. The therapeutic effects of hAECs on lung fibrosis are attributed to many factors. We performed a systematic review of preclinical studies investigating the treatment of pulmonary fibrosis with hAECs to provide suggestions for their clinical use...
2018: PloS One
https://www.readbyqxmd.com/read/29771487/cancer-cell-membrane-coated-adjuvant-nanoparticles-with-mannose-modification-for-effective-anticancer-vaccination
#6
Rong Yang, Jun Xu, Ligeng Xu, Xiaoqi Sun, Qian Chen, Yuhuan Zhao, Rui Peng, Zhuang Liu
Tumor vaccines for cancer prevention and treatment have attracted tremendous interests in the area of cancer immunotherapy in recent years. In this work, we present a strategy to construct cancer vaccines by encapsulating immune-adjuvant nanoparticles with cancer cell membrane modified by mannose. Poly (D, L-lactide-co-glycolide) (PLGA) nanoparticles are firstly loaded with toll-like receptor 7 agonist, imiquimod (R837). Those adjuvant nanoparticles (NP-R) are then coated with cancer cell membranes (NP-R@M), whose surface proteins could act as tumor-specific antigens...
May 17, 2018: ACS Nano
https://www.readbyqxmd.com/read/29763906/the-therapeutic-effect-of-icam-1-overexpressing-mesenchymal-stem-cells-on-acute-graft-versus-host-disease
#7
Bo Tang, Xue Li, Yuanlin Liu, Xiuhui Chen, Ximei Li, Yanan Chu, Heng Zhu, Weijiang Liu, Fenfen Xu, Fan Zhou, Yi Zhang
BACKGROUND/AIMS: Mesenchymal stem cells (MSCs) do not readily migrate to appropriate sites, and this creates a major obstacle for their use in the treatment of graft-versus-host disease (GVHD). Intercellular adhesion molecule-1 (ICAM-1) can guide the homing of various immune cells to the proper anatomical location within secondary lymphoid organs (SLOs), which are the major niches for generating immune responses or tolerance. MSCs rarely migrate to SLOs after intravenous infusion, and are constitutively low expression of ICAM-1...
May 7, 2018: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29761344/beyond-the-magic-bullet-current-progress-of-therapeutic-vaccination-in-multiple-sclerosis
#8
Barbara Willekens, Nathalie Cools
Multiple sclerosis (MS) is a chronic immune-mediated disease of the central nervous system (CNS) characterized by neuroinflammation, neurodegeneration and impaired repair mechanisms that lead to neurological disability. The crux of MS is the patient's own immune cells attacking self-antigens in the CNS, namely the myelin sheath that protects nerve cells of the brain and spinal cord. Restoring antigen-specific tolerance via therapeutic vaccination is an innovative and exciting approach in MS therapy. Indeed, leveraging the body's attempt to prevent autoimmunity, i...
May 14, 2018: CNS Drugs
https://www.readbyqxmd.com/read/29755954/immune-response-generated-with-the-administration-of-autologous-dendritic-cells-pulsed-with-an-allogenic-tumoral-cell-lines-lysate-in-patients-with-newly-diagnosed-diffuse-intrinsic-pontine-glioma
#9
Daniel Benitez-Ribas, Raquel Cabezón, Georgina Flórez-Grau, Mari Carmen Molero, Patricia Puerta, Antonio Guillen, Sonia Paco, Angel M Carcaboso, Vicente Santa-Maria Lopez, Ofelia Cruz, Carmen de Torres, Noelia Salvador, Manel Juan, Jaume Mora, Andres Morales La Madrid
Background and objective: Diffuse intrinsic pontine glioma (DIPG) is a lethal brainstem tumor in children. Dendritic cells (DCs) have T-cell stimulatory capacity and, therefore, potential antitumor activity for disease control. DCs vaccines have been shown to reactivate tumor-specific T cells in both clinical and preclinical settings. We designed a phase Ib immunotherapy (IT) clinical trial with the use of autologous dendritic cells (ADCs) pulsed with an allogeneic tumors cell-lines lysate in patients with newly diagnosed DIPG after irradiation (radiation therapy)...
2018: Frontiers in Oncology
https://www.readbyqxmd.com/read/29751951/biochemical-characterization-and-immunogenicity-of-neureight-a-recombinant-full-length-factor-viii-produced-by-fed-batch-process-in-disposable-bioreactors
#10
Sandrine Delignat, Ivan Peyron, Maria El Ghazaly, Srinivas V Kaveri, Jan Rohde, Frank Mueller, Sebastien Lacroix-Desmazes
Hemophilia A is a X-linked recessive bleeding disorder consecutive to the lack of circulating pro-coagulant factor VIII (FVIII). The most efficient strategy to treat or prevent bleeding in patients with hemophilia A relies on replacement therapy using exogenous FVIII. Commercially available recombinant FVIII are produced using an expensive perfusion technology in stainless steel fermenters. A fed-batch fermentation technology was recently developed to produce 'Neureight', a full-length recombinant human FVIII, in Chinese hamster ovary (CHO) cells...
May 5, 2018: Cellular Immunology
https://www.readbyqxmd.com/read/29746296/pd-1-contributes-to-the-establishment-and-maintenance-of-hiv-1-latency
#11
Vanessa A Evans, Renée M Van Der Sluis, Ajantha Solomon, Ashanti Dantanarayana, Catriona McNeil, Roger Garsia, Sarah Palmer, Rémi Fromentin, Nicolas Chomont, Rafick-Pierre Sékaly, Paul U Cameron, Sharon R Lewin
OBJECTIVE: In HIV-infected individuals on antiretroviral therapy (ART), latent HIV is enriched in CD4 T-cells expressing immune checkpoint molecules (ICs), in particular programmed cell death-1 (PD-1). We therefore assessed the effect of blocking PD-1 on latency, both in vitro and in vivo. METHODS: HIV latency was established in vitro following co-culture of resting CD4 T-cells with myeloid dendritic cells. Expression of PD-1 was quantified by flow cytometry, and latency assessed in sorted PD-1 and PD-1 non-proliferating CD4 memory T-cells...
May 9, 2018: AIDS
https://www.readbyqxmd.com/read/29738575/adoptive-transfer-of-dendritic-cells-expressing-cd11c-reduces-the-immunological-response-associated-with-experimental-colitis-in-balb-c-mice
#12
Lisiery N Paiatto, Fernanda G D Silva, Áureo T Yamada, Wirla M S C Tamashiro, Patricia U Simioni
INTRODUCTION: In addition to conventional therapies, several new strategies have been proposed for modulating autoimmune diseases, including the adoptive transfer of immunological cells. In this context, dendritic cells (DCs) appear to be one of the most promising treatments for autoimmune disorders. The present study aimed to evaluate the effects of adoptive transfer of DCs obtained from both naïve and ovalbumin (OVA)-tolerant mice on the severity of TNBS induced colitis and analyze the eventual protective mechanisms...
2018: PloS One
https://www.readbyqxmd.com/read/29738228/enhanced-tumor-retention-effect-by-click-chemistry-for-improved-cancer-immunochemotherapy
#13
Ling Mei, Yayuan Liu, Jingdong Rao, Xian Tang, Man Li, Zhirong Zhang, Qin He
Due to the limited drug concentration in tumor tissues and inappropriate treatment strategies, tumor recurrence and metastasis are critical challenges for effectively treating malignancies. A key challenge for effective delivery of nanoparticles is to reduce reticuloendothelial system uptake and to maximize the enhanced permeability and retention effect. Herein, we demonstrated that Cu(I)-catalyzed click chemistry triggered the aggregation of azide/alkyne-modified micelles, enhancing micelles accumulation in tumor tissues...
May 8, 2018: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/29735668/modeling-combination-therapy-for-breast-cancer-with-bet-and-immune-checkpoint-inhibitors
#14
Xiulan Lai, Andrew Stiff, Megan Duggan, Robert Wesolowski, William E Carson, Avner Friedman
CTLA-4 is an immune checkpoint expressed on active anticancer T cells. When it combines with its ligand B7 on dendritic cells, it inhibits the activity of the T cells. The Bromo- and Extra-Terminal (BET) protein family includes proteins that regulate the expression of key oncogenes and antiapoptotic proteins. BET inhibitor (BETi) has been shown to reduce the expression of MYC by suppressing its transcription factors and to down-regulate the hypoxic transcriptome response to VEGF-A. This paper develops a mathematical model of the treatment of cancer by combination therapy of BETi and CTLA-4 inhibitor...
May 7, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29733389/temozolomide-for-immunomodulation-in-the-treatment-of-glioblastoma
#15
Aida Karachi, Farhad Dastmalchi, Duane Mitchell, Maryam Rahman
Temozolomide is the most widely used chemotherapy for patients with glioblastoma (GBM) despite the fact that approximately half of treated patients have temozolomide resistance and all patients eventually fail therapy. Due to the limited efficacy of existing therapies, immunotherapy is being widely investigated for patients with GBM. However, initial immunotherapy trials in GBM patients have had disappointing results as monotherapy. Therefore, combinatorial treatment strategies are being investigated. Temozolomide has several effects on the immune system that are dependent on mode of delivery and the dosing strategy that may have unpredicted effects on immunotherapy...
May 4, 2018: Neuro-oncology
https://www.readbyqxmd.com/read/29730556/new-peptide-my1340-revert-the-inhibition-effect-of-vegf-on-dendritic-cells-differentiation-and-maturation-via-blocking-vegf-nrp-1-axis-and-inhibit-tumor-growth-in-vivo
#16
Zheng Mo, Fei Yu, Su Han, Songhua Yang, Liangliang Wu, Peng Li, Shunchang Jiao
The development and clinical application of immunostimulatory therapy provides us a new and exciting strategy in cancer treatment of which the agents act on crucial receptors. Given the fact that Neuropilin-1(NRP-1) is essential for vascular endothelial growth factor (VEGF) to inhibit LPS-dependent maturation of dendritic cells (DCs), it may present a potentially meaningful target in cancer immunotherapy. To explore this hypothesis, we synthesized a novel polypeptide called MY1340 consist of 32 amino acids with the aim of targeting VEGF-NRP-1 axis...
May 3, 2018: International Immunopharmacology
https://www.readbyqxmd.com/read/29729445/emerging-role-of-il-35-in-inflammatory-autoimmune-diseases
#17
REVIEW
Lin-Chong Su, Xiao-Yan Liu, An-Fang Huang, Wang-Dong Xu
Interleukin 35 (IL-35) is the recently identified member of the IL-12 family of cytokines and provides the possibility to be a target for new therapies for autoimmune, inflammatory diseases. It is composed of an α chain (p35) and a β chain (EBI3). IL-35 mediates signaling by binding to its receptors, activates subsequent signaling pathways, and therefore, regulates the differentiation, function of T, B cells, macrophages, dendritic cells. Recent findings have shown abnormal expression of IL-35 in inflammatory autoimmune diseases, such as systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, multiple sclerosis, type 1 diabetes, psoriasis, multiple sclerosis, autoimmune hepatitis, experimental autoimmune uveitis...
May 3, 2018: Autoimmunity Reviews
https://www.readbyqxmd.com/read/29725333/follicular-dendritic-cells-of-lymph-nodes-as-human-immunodeficiency-virus-simian-immunodeficiency-virus-reservoirs-and-insights-on-cervical-lymph-node
#18
REVIEW
Rajnish S Dave, Pooja Jain, Siddappa N Byrareddy
A hallmark feature of follicular dendritic cells (FDCs) within the lymph nodes (LNs) is their ability to retain antigens and virions for a prolonged duration. FDCs in the cervical lymph nodes (CLNs) are particularly relevant in elucidating human immunodeficiency virus (HIV)-1 infection within the cerebrospinal fluid (CSF) draining LNs of the central nervous system. The FDC viral reservoir in both peripheral LN and CLN, like the other HIV reservoirs, contribute to both low-level viremia and viral resurgence upon cessation or failure of combined antiretroviral therapy (cART)...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29725327/lymph-node-cellular-and-viral-dynamics-in-natural-hosts-and-impact-for-hiv-cure-strategies
#19
REVIEW
Nicolas Huot, Steven E Bosinger, Mirko Paiardini, R Keith Reeves, Michaela Müller-Trutwin
Combined antiretroviral therapies (cARTs) efficiently control HIV replication leading to undetectable viremia and drastic increases in lifespan of people living with HIV. However, cART does not cure HIV infection as virus persists in cellular and anatomical reservoirs, from which the virus generally rebounds soon after cART cessation. One major anatomical reservoir are lymph node (LN) follicles, where HIV persists through replication in follicular helper T cells and is also trapped by follicular dendritic cells...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29724512/initial-phase-i-iia-trial-results-of-an-autologous-tumor-lysate-particle-loaded-dendritic-cell-tlpldc-vaccine-in-patients-with-solid-tumors
#20
Garth S Herbert, Timothy J Vreeland, Guy T Clifton, Julia M Greene, Doreen O Jackson, Mark O Hardin, Diane F Hale, John S Berry, Pauline Nichol, Sook Yin, Xianzhong Yu, Thomas E Wagner, George E Peoples
INTRODUCTION: Tumor vaccines use various strategies to generate immune responses, commonly targeting generic tumor-associated antigens. The tumor lysate, particle-loaded, dendritic cell (TLPLDC) vaccine is produced from DC loaded with autologous tumor antigens, creating a patient-specific vaccine. Here, we describe initial phase I/IIa trial results. METHODS: This trial includes patients with any stage solid tumors, ECOG ≤1, and >4 months life-expectancy. A personalized vaccine is created using 1 mg of tumor and 120 ml blood (to isolate DC)...
April 30, 2018: Vaccine
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