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https://www.readbyqxmd.com/read/27919753/advax-a-delta-inulin-microparticle-potentiates-in-built-adjuvant-property-of-co-administered-vaccines
#1
Masayuki Hayashi, Taiki Aoshi, Yasunari Haseda, Kouji Kobiyama, Edward Wijaya, Noriyuki Nakatsu, Yoshinobu Igarashi, Daron M Standley, Hiroshi Yamada, Yoshikazu Honda-Okubo, Hiromitsu Hara, Takashi Saito, Toshiyuki Takai, Cevayir Coban, Nikolai Petrovsky, Ken J Ishii
Advax, a delta inulin-derived microparticle, has been developed as an adjuvant for several vaccines. However, its immunological characteristics and potential mechanism of action are yet to be elucidated. Here, we show that Advax behaves as a type-2 adjuvant when combined with influenza split vaccine, a T helper (Th)2-type antigen, but behaves as a type-1 adjuvant when combined with influenza inactivated whole virion (WV), a Th1-type antigen. In addition, an adjuvant effect was not observed when Advax-adjuvanted WV vaccine was used to immunize toll-like receptor (TLR) 7 knockout mice which are unable to respond to RNA contained in WV antigen...
December 1, 2016: EBioMedicine
https://www.readbyqxmd.com/read/27916138/alcohol-exposure-differentially-effects-anti-tumor-immunity-in-females-by-altering-dendritic-cell-function
#2
Matthew G Thompson, Flor Navarro, Lennox Chitsike, Luis Ramirez, Elizabeth J Kovacs, Stephanie K Watkins
Dendritic cells (DCs) are a critical component of anti-tumor immunity due to their ability to induce a robust immune response to antigen (Ag). Alcohol was previously shown to reduce DC ability to present foreign Ag and promote pro-inflammatory responses in situations of infection and trauma. However the impact of alcohol exposure on generation of an anti-tumor response, especially in the context of generation of an immune vaccine has not been examined. In the clinic, DC vaccines are typically generated from autologous blood, therefore prior exposure to substances such as alcohol may be a critical factor to consider regarding the effectiveness in generating an immune response...
December 2016: Alcohol
https://www.readbyqxmd.com/read/27914453/myeloid-derived-suppressor-cells-and-proinflammatory-cytokines-as-targets-for-cancer-therapy
#3
REVIEW
K-S N Atretkhany, M S Drutskaya
Myeloid-derived suppressor cells represent a heterogeneous population of immature myeloid cells. Under normal conditions, these cells differentiate into macrophages, dendritic cells, and granulocytes. However, in pathological states such as inflammation, infection, or tumor growth, there is an arrest of their differentiation that results in the accumulation of immature myeloid cells in the organism. In addition, these cells acquire a suppressor phenotype, expressing anti-inflammatory cytokines and reactive oxygen and nitrogen species, and suppress T-cell immune response...
November 2016: Biochemistry. Biokhimii︠a︡
https://www.readbyqxmd.com/read/27910859/t-cell-programming-in-pancreatic-adenocarcinoma-a-review
#4
REVIEW
Y D Seo, V G Pillarisetty
Despite recent advancements in multimodal therapy, pancreatic ductal adenocarcinoma (PDA) continues to have a dismal prognosis. In the era of burgeoning immune therapies against previously difficult-to-treat malignancies, there has been growing interest in activating the immune system against PDA; however, unlike in other cancers such as melanoma and lymphoma, immunotherapy has not yielded many clinically significant results. To harness these mechanisms for therapeutic use, an in-depth understanding of T-cell programming in the immune microenvironment of PDA must be achieved...
December 2, 2016: Cancer Gene Therapy
https://www.readbyqxmd.com/read/27906162/activation-of-myeloid-and-endothelial-cells-by-cd40l-gene-therapy-supports-t-cell-expansion-and-migration-into-the-tumor-microenvironment
#5
E Eriksson, R Moreno, I Milenova, L Liljenfeldt, L C Dieterich, L Christiansson, H Karlsson, G Ullenhag, S Mangsbo, A Dimberg, R Alemany, A Loskog
CD40 is an interesting target in cancer immunotherapy due to its ability to stimulate Th1 immunity via maturation of dendritic cells and to drive M2 to M1 macrophage differentiation. Pancreatic cancer has a high M2 content that has shown responsive to anti-CD40 agonist therapy and CD40 may thus be a suitable target for immune activation in these patients. In this study, a novel oncolytic adenovirus armed with a trimerized membrane-bound extracellular CD40L (TMZ-CD40L) was evaluated as a treatment of pancreatic cancer...
December 1, 2016: Gene Therapy
https://www.readbyqxmd.com/read/27904768/combined-vegfr-and-ctla-4-blockade-increases-the-antigen-presenting-function-of-intratumoral-dcs-and-reduces-the-suppressive-capacity-of-intratumoral-mdscs
#6
Stephanie Du Four, Sarah K Maenhout, Simone P Niclou, Kris Thielemans, Bart Neyns, Joeri L Aerts
Melanoma brain metastases (MBM) occur in 10% to 50% of melanoma patients. They are often associated with a high morbidity and despite the improvements in the treatment of advanced melanoma, including immunotherapy, patients with MBM still have a poor prognosis. Antiangiogenic treatment was shown to reduce the immunosuppressive tumor microenvironment. Therefore we investigated the effect of the combination of VEGFR- and CTLA-4 blockade on the immune cells within the tumor microenvironment. In this study we investigated the effect of the combination of axitinib, a TKI against VEGFR-1, -2 and -3, with therapeutic inhibition of CTLA-4 in subcutaneous and intracranial mouse melanoma models...
2016: American Journal of Cancer Research
https://www.readbyqxmd.com/read/27901642/a-generic-rna-pulsed-dc-based-approach-for-developing-therapeutic-intervention-against-nasopharyngeal-carcinoma
#7
Rajeev K Tyagi, Rajesh Parmar, Naisargee Patel
The recurrent nasopharyngeal carcinoma of head-and-neck cancers pathology showed unique symptoms and clinical characteristics. The complexity of pathology poses challenges for developing therapeutic interventional approaches against nasopharyngeal carcinoma (NPC). The conventional treatment regimens offer limited local control and survival, which, leads to adverse delayed complications. Our study present a generic monocyte derived dendritic cell (MoDC) vaccine strategy for NPC in which RNA is used as a source of tumor-associated antigens (TAAgs)...
November 30, 2016: Human Vaccines & Immunotherapeutics
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
#8
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/27895816/clinical-impact-of-chemotherapy-to-improve-tumor-microenvironment-of-pancreatic-cancer
#9
REVIEW
Takahiro Tsuchikawa, Shintaro Takeuchi, Toru Nakamura, Toshiaki Shichinohe, Satoshi Hirano
A perioperative multimodal strategy including combination chemotherapy and radiotherapy, in addition to surgical resection, has been acknowledged to improve patient prognosis. However chemotherapy has not been actively applied as an immunomodulating modality because of concerns about various immunosuppressive effects. It has recently been shown that certain chemotherapeutic agents could modify tumor microenvironment and host immune responses through several underlying mechanisms such as immunogenic cell death, local T-cell infiltration and also the eradication of immune-suppressing regulatory cells such as regulatory T cells (Tregs) and myeloid-derived suppressor cells...
November 15, 2016: World Journal of Gastrointestinal Oncology
https://www.readbyqxmd.com/read/27895398/dysregulation-of-innate-immunity-in-ulcerative-colitis-patients-who-fail-anti-tumor-necrosis-factor-therapy
#10
Angela C Baird, Dominic Mallon, Graham Radford-Smith, Julien Boyer, Thierry Piche, Susan L Prescott, Ian C Lawrance, Meri K Tulic
AIM: To study the innate immune function in ulcerative colitis (UC) patients who fail to respond to anti-tumor necrosis factor (TNF) therapy. METHODS: Effects of anti-TNF therapy, inflammation and medications on innate immune function were assessed by measuring peripheral blood mononuclear cell (PBMC) cytokine expression from 18 inflammatory bowel disease patients pre- and 3 mo post-anti-TNF therapy. Toll-like receptor (TLR) expression and cytokine production post TLR stimulation was assessed in UC "responders" (n = 12) and "non-responders" (n = 12) and compared to healthy controls (n = 12)...
November 7, 2016: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/27889516/lenalidomide-enhances-the-function-of-dendritic-cells-generated-from-patients-with-multiple-myeloma
#11
Manh-Cuong Vo, Truc Anh-NguyenThi, Hyun-Ju Lee, Thanh-Nhan Nguyen-Pham, Thangaraj Jaya Lakshmi, Sung-Hoon Jung, Hyeoung-Joon Kim, Je-Jung Lee
Lenalidomide (LEN) has been used as an immunomodulatory drug with direct and indirect anti-tumor effects. In this study, we evaluated the effect of LEN on the differentiation, maturation, and function of dendritic cells (DCs) in patients with multiple myeloma (MM) in vitro. Various doses of LEN were added after the monocytes had differentiated into immature DCs (imDCs) and activated into mature DCs (mDCs). LEN (5 μg/mL) was the optimal concentration to promote differentiation and maturation of DCs. imDCs treated with LEN showed enhanced endocytic capacity...
November 23, 2016: Experimental Hematology
https://www.readbyqxmd.com/read/27879151/overcoming-drug-resistance-with-on-demand-charged-thermoresponsive-dendritic-nanogels
#12
Maria Molina, Stefanie Wedepohl, Enrico Miceli, Marcelo Calderón
AIM: To develop nanogels (NG) able to modulate the encapsulation and release of drugs, in order to circumvent drug resistance mechanisms in cancer cells. MATERIALS & METHODS: Poly-N-isopropylacrylamide-dendritic polyglycerol NG were semi-interpenetrated with 2-acrylamido-2-methylpropane sulfonic acid or (2-dimethylamino) ethyl methacrylate. Physico-chemical properties of the NGs as well as doxorubicin (DOXO) loading and release were characterized. Drug delivery performance was investigated in vitro and in vivo in a multidrug-resistant tumor model...
November 23, 2016: Nanomedicine
https://www.readbyqxmd.com/read/27878306/effects-of-interleukin-1-receptor-associated-kinase%C3%A2-1-rna-interference-in-dendritic-cells-on-inflammatory-cytokine-release-and-t-cell-proliferation
#13
Yan Gao, Xuxu Xu, Juan Feng, Ying Ma, Dongming Zheng, Yiming Meng, Fengping Shan
The present study aimed to reduce the expression of interleukin-1 receptor-associated kinase 1 (IRAK-1) in dendritic cells (DCs) by RNA interference (RNAi). Subsequently, its effects on the expression of costimulatory surface molecules, the release of inflammatory cytokines, and the proliferation of T cells during the activation process of DCs, were determined. RNAi was used to silence IRAK‑1 gene expression in DCs, followed by lipopolysaccharide stimulation. Flow cytometry was then used to detect the expression levels of DC surface molecules, including cluster of differentiation (CD)86, major histocompatibility complex class II and CD40...
November 15, 2016: Molecular Medicine Reports
https://www.readbyqxmd.com/read/27875974/nanoparticle-systems-modulating-myeloid-derived-suppressor-cells-for-cancer-immunotherapy
#14
Avia Wilkerson, Julian Kim, Alex Y Huang, Mei Zhang
Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of immature myeloid cells that are preferentially expanded in cancer. They arise from myeloid progenitor cells that do not differentiate into mature dendritic cells (DCs), granulocytes, or macrophages, and are rather thought to play a pivotal role in immune escape and cancer progression. MDSCs are characterized by the ability to suppress T cell proliferation and cytotoxicity, inhibit natural killer T (NKT) cell activation, and induce the differentiation and expansion of regulatory T cells (Treg)...
November 22, 2016: Current Topics in Medicinal Chemistry
https://www.readbyqxmd.com/read/27875627/immunotherapy-approaches-in-the-treatment-of-malignant-brain-tumors
#15
REVIEW
Anastasie M Dunn-Pirio, Gordana Vlahovic
Glioblastoma is the most common malignant primary brain tumor. Despite standard-of-care treatment, consisting of maximal surgical resection followed by chemoradiation, both morbidity and mortality associated with this disease remain very poor. Therefore, there is an urgent need for more efficacious and well tolerated therapies. Advancing knowledge of the intricate interplay between malignant gliomas and the immune system, coupled with the recent launch of immunotherapy research for other cancers, has led to a veritable increase in immunotherapy investigation for glioblastoma and other malignant gliomas...
November 22, 2016: Cancer
https://www.readbyqxmd.com/read/27874015/metabolic-sialic-acid-blockade-lowers-the-activation-threshold-of-modcs-for-tlr-stimulation
#16
Christian Büll, Estel Collado-Camps, Esther D Kers-Rebel, Torben Heise, Jonas N Søndergaard, Martijn H den Brok, Barbara M Schulte, Thomas J Boltje, Gosse J Adema
Sialic acid sugars cover the surface of dendritic cells (DCs) and have been suggested to impact several aspects of DC biology. Research into the role of sialic acids in DCs, however, is complicated by the limited number of tools available to modulate sialic acid expression. Here we report on a synthetic, fluorinated sialic acid mimetic, Ac53FaxNeu5Ac, which potently blocks sialic acid expression in human monocyte-derived DCs (moDCs). Sialic acid blockade enhanced the responsiveness of moDCs to Toll-like receptor (TLR) stimulation as measured by increased maturation marker expression and cytokine production...
November 22, 2016: Immunology and Cell Biology
https://www.readbyqxmd.com/read/27873505/hyperbaric-oxygen-pretreatment-improves-cognition-and-reduces-hippocampal-damage-via-p38-mitogen-activated-protein-kinase-in-a-rat-model
#17
Baisong Zhao, Yongying Pan, Zixin Wang, Haiping Xu, Xingrong Song
PURPOSE: To investigate the effects of hyperbaric oxygen (HBO) pretreatment on cognitive decline and neuronal damage in an Alzheimer's disease (AD) rat model. MATERIALS AND METHODS: Rats were divided into three groups: normal saline (NS), AD, and HBO+AD. In the AD group, amyloid β peptide (Aβ)₁₋₄₀ was injected into the hippocampal CA1 region of the brain. NS rats received NS injection. In the HBO+AD group, rats received 5 days of daily HBO therapy following Aβ₁₋₄₀ injection...
January 2017: Yonsei Medical Journal
https://www.readbyqxmd.com/read/27872905/interferon-driven-deletion-of-antiviral-b-cells-at-the-onset-of-chronic-infection
#18
Benedict Fallet, Kerstin Narr, Yusuf I Ertuna, Melissa Remy, Rami Sommerstein, Karen Cornille, Mario Kreutzfeldt, Nicolas Page, Gert Zimmer, Florian Geier, Tobias Straub, Hanspeter Pircher, Kevin Larimore, Philip D Greenberg, Doron Merkler, Daniel D Pinschewer
Inadequate antibody responses and perturbed B cell compartments represent hallmarks of persistent microbial infections, but the mechanisms whereby persisting pathogens suppress humoral immunity remain poorly defined. Using adoptive transfer experiments in the context of a chronic lymphocytic choriomeningitis virus (LCMV) infection of mice, we have documented rapid depletion of virus-specific B cells that coincided with the early type I interferon response to infection. We found that the loss of activated B cells was driven by type I interferon (IFN-I) signaling to several cell types including dendritic cells, T cells and myeloid cells...
October 21, 2016: Science Immunology
https://www.readbyqxmd.com/read/27872213/autocrine-type-i-ifn-signaling-in-dendritic-cells-stimulated-with-fungal-%C3%AE-glucans-or-lipopolysaccharide-promotes-cd8-t-cell-activation
#19
Nargess Hassanzadeh-Kiabi, Alberto Yáñez, Ivy Dang, Gislâine A Martins, David M Underhill, Helen S Goodridge
Type I IFNs are key mediators of immune defense against viruses and bacteria. Type I IFNs were also previously implicated in protection against fungal infection, but their roles in antifungal immunity have not been thoroughly investigated. A recent study demonstrated that bacterial and fungal β-glucans stimulate IFN-β production by dendritic cells (DCs) following detection by the Dectin-1 receptor, but the effects of β-glucan-induced type I IFNs have not been defined. We investigated whether type I IFNs regulate CD8 T cell activation by fungal β-glucan particle-stimulated DCs...
November 21, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27870961/design-and-construction-of-multifunctional-hyperbranched-polymers-coated-magnetite-nanoparticles-for-both-targeting-magnetic-resonance-imaging-and-cancer-therapy
#20
Asemeh Mashhadi Malekzadeh, Ali Ramazani, Seyed Jamal Tabatabaei Rezaei, Hassan Niknejad
Magnetic drug targeting is a drug delivery strategy that can be used to improve the therapeutic efficiency on tumor cells and reduce the side effects on normal cells and tissues. The aim in this study is designing a novel multifunctional drug delivery system based on superparamagnetic nanoparticles for cancer therapy. Magnetic nanoparticles were synthesized by coprecipitation of iron oxide followed by coating with poly citric acid (PCA) dendritic macromolecules via bulk polymerization strategy. It was further surface-functionalized with poly(ethylene glycol) (PEG) and then to achieve tumor cell targeting property, folic acid was further incorporated to the surface of prepared carriers via a facile coupling reaction between the hydroxyl end group of the PEG and the carboxyl group of folic acid...
November 10, 2016: Journal of Colloid and Interface Science
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