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Dendritic cell immunotherapy

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https://www.readbyqxmd.com/read/28214225/a-relay-pathway-between-arginine-and-tryptophan-metabolism-confers-immunosuppressive-properties-on-dendritic-cells
#1
Giada Mondanelli, Roberta Bianchi, Maria Teresa Pallotta, Ciriana Orabona, Elisa Albini, Alberta Iacono, Maria Laura Belladonna, Carmine Vacca, Francesca Fallarino, Antonio Macchiarulo, Stefano Ugel, Vincenzo Bronte, Federica Gevi, Lello Zolla, Auke Verhaar, Maikel Peppelenbosch, Emilia Maria Cristina Mazza, Silvio Bicciato, Yasmina Laouar, Laura Santambrogio, Paolo Puccetti, Claudia Volpi, Ursula Grohmann
Arginase 1 (Arg1) and indoleamine 2,3-dioxygenase 1 (IDO1) are immunoregulatory enzymes catalyzing the degradation of l-arginine and l-tryptophan, respectively, resulting in local amino acid deprivation. In addition, unlike Arg1, IDO1 is also endowed with non-enzymatic signaling activity in dendritic cells (DCs). Despite considerable knowledge of their individual biology, no integrated functions of Arg1 and IDO1 have been reported yet. We found that IDO1 phosphorylation and consequent activation of IDO1 signaling in DCs was strictly dependent on prior expression of Arg1 and Arg1-dependent production of polyamines...
February 13, 2017: Immunity
https://www.readbyqxmd.com/read/28205361/immunotherapy-against-metastatic-bladder-cancer-by-combined-administration-of-granulocyte-macrophage-colony-stimulating-factor-and-interleukin-2-surface-modified-mb49-bladder-cancer-stem-cells-vaccine
#2
Chun-Yan Wang, Rui Hua, Li Liu, Xiaomin Zhan, Simei Chen, Song Quan, Qing-Jun Chu, Yong-Tong Zhu
In previous studies, it has been shown that the granulocyte macrophage-colony stimulating factor (GM-CSF) or interleukin-2 (IL-2) surface modified MB49 bladder cancer stem cells (MCSCs) vaccine could induce a specific antitumor immunity and against bladder cancer in mice model respectively. However, whether combined administration of GM-CSF and IL-2 could produce specific immune responses to cancer stem cells (CSCs) was uncertain. MCSCs were established and characterized. GM-CSF and IL-2 MCSCs vaccines were prepared and bioactivity was evaluated...
February 16, 2017: Cancer Medicine
https://www.readbyqxmd.com/read/28203287/specific-immunotherapy-in-renal-cancer-a-systematic-review
#3
REVIEW
Armin Hirbod-Mobarakeh, Hesam Addin Gordan, Zahra Zahiri, Mohammad Mirshahvalad, Sima Hosseinverdi, Brian I Rini, Nima Rezaei
BACKGROUND: Renal cell cancer (RCC) is the tenth most common malignancy in adults. In recent years, several approaches of active and passive immunotherapy have been studied extensively in clinical trials of patients with RCC. The aim of this systematic review was to assess the clinical efficacy of various approaches of specific immunotherapy in patients with RCC. METHODS: We searched Medline, Scopus, CENTRAL, TRIP, DART, OpenGrey and ProQuest without any language filter through to 9 October 2015...
February 2017: Therapeutic Advances in Urology
https://www.readbyqxmd.com/read/28201977/targeting-the-immune-niche-within-the-bone-marrow-microenvironment-the-rise-of-immunotherapy-in-multiple-myeloma
#4
Klaus Podar, D Jäger
Multiple Myeloma (MM) cells inhibit the development of an effective anti-MM immune response via defects in T cell function, ineffective antigen presentation; reduced phagocytic capacity; natural killer and dendritic cell dysfunction; decreased responsiveness to IL-2 and defects in B cell immunity; upregulation of inhibitory pathways; and production of excessive pro-inflammatory cytokines. Moreover, immune cells including plasmacytoid dendritic cells and macrophages trigger tumor cell proliferation, survival, and drug resistance...
February 13, 2017: Current Cancer Drug Targets
https://www.readbyqxmd.com/read/28197373/systemic-activation-of-antigen-presenting-cells-via-rna-loaded-nanoparticles
#5
Elias J Sayour, Gabriel De Leon, Christina Pham, Adam Grippin, Hanna Kemeny, Joshua Chua, Jianping Huang, John H Sampson, Luis Sanchez-Perez, Catherine Flores, Duane A Mitchell
While RNA-pulsed dendritic cell (DC) vaccines have shown promise, the advancement of cellular therapeutics is fraught with developmental challenges. To circumvent the challenges of cellular immunotherapeutics, we developed clinically translatable nanoliposomes that can be combined with tumor-derived RNA to generate personalized tumor RNA-nanoparticles (NPs) with considerable scale-up capacity. RNA-NPs bypass MHC restriction, are amenable to central distribution, and can provide near immediate immune induction...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28192720/dendritic-cells-in-cancer-the-role-revisited
#6
REVIEW
Filippo Veglia, Dmitry I Gabrilovich
Dendritic cells (DCs) with their potent antigen presenting ability are long considered as critical factor in antitumor immunity. Despite high potential in promoting antitumor responses, tumor-associated DCs are largely defective in their functional activity and can contribute to immune suppression in cancer. In recent years existence of immune suppressive regulatory DCs in tumor microenvironment was described. Monocytic myeloid derived suppressor cells (M-MDSCs) can contribute to the pool of tumor associated DCs by differentiating to inflammatory DCs (inf-DCs), which appear to have specific phenotype and is critical component of antitumor response...
February 10, 2017: Current Opinion in Immunology
https://www.readbyqxmd.com/read/28191816/interferon-%C3%AE-inducible-dendritic-cells-matured-with-ok-432-exhibit-trail-and-fas-ligand-pathway-mediated-killer-activity
#7
Terutsugu Koya, Ryu Yanagisawa, Yumiko Higuchi, Kenji Sano, Shigetaka Shimodaira
Active human dendritic cells (DCs), which efficiently induce immune responses through their functions as antigen-presenting cells, exhibit direct anti-tumour killing activity in response to some pathogens and cytokines. These antigen-presenting and tumour killing abilities may provide a breakthrough in cancer immunotherapy. However, the mechanisms underlying this killer DC activity have not been fully proven, despite the establishment of interferon-α (IFN-α)-generated killer DCs (IFN-DCs). Here mature IFN-DCs (mIFN-DCs), generated from IFN-DCs primed with OK-432 (streptococcal preparation), exhibited elevated expression of CD86 and human leukocyte antigen-DR (minimum criteria for DC vaccine clinical trials) as well as antigen-presenting abilities comparable with those of mature IL-4-DCs (mIL-4-DCs)...
February 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28187172/generation-of-dendritic-cell-based-vaccine-using-high-hydrostatic-pressure-for-non-small-cell-lung-cancer-immunotherapy
#8
Nada Hradilova, Lenka Sadilkova, Ondrej Palata, Dagmar Mysikova, Hana Mrazkova, Robert Lischke, Radek Spisek, Irena Adkins
High hydrostatic pressure (HHP) induces immunogenic death of tumor cells which confer protective anti-tumor immunity in vivo. Moreover, DC pulsed with HHP-treated tumor cells induced therapeutic effect in mouse cancer model. In this study, we tested the immunogenicity, stability and T cell stimulatory activity of human monocyte-derived dendritic cell (DC)-based HHP lung cancer vaccine generated in GMP compliant serum free medium using HHP 250 MPa. DC pulsed with HHP-killed lung cancer cells and poly(I:C) enhanced DC maturation, chemotactic migration and production of pro-inflammatory cytokines after 24h...
2017: PloS One
https://www.readbyqxmd.com/read/28186996/harnessing-rna-sequencing-for-global-unbiased-evaluation-of-two-new-adjuvants-for-dendritic-cell-immunotherapy
#9
Till S M Mathan, Johannes Textor, Annette E Sköld, Inge Reinieren-Beeren, Tom van Oorschot, Mareke Brüning, Carl G Figdor, Sonja I Buschow, Ghaith Bakdash, I Jolanda M de Vries
Effective stimulation of immune cells is crucial for the success of cancer immunotherapies. Current approaches to evaluate the efficiency of stimuli are mainly defined by known flow cytometry-based cell activation or cell maturation markers. This method however does not give a complete overview of the achieved activation state and may leave important side effects unnoticed. Here, we used an unbiased RNA sequencing (RNA-seq)-based approach to compare the capacity of four clinical-grade dendritic cell (DC) activation stimuli used to prepare DC-vaccines composed of various types of DC subsets; the already clinically applied GM-CSF and Frühsommer meningoencephalitis (FSME) prophylactic vaccine and the novel clinical grade adjuvants protamine-RNA complexes (pRNA) and CpG-P...
February 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28186088/current-status-of-immunotherapy-for-gastrointestinal-stromal-tumor
#10
REVIEW
Y Tan, J C Trent, B A Wilky, D A Kerr, A E Rosenberg
Gastrointestinal stromal tumors (GIST) contain tumor-infiltrating immune cells and their presence provides an opportunity and rationale for developing effective forms of immunotherapy. The types of tumor-infiltrating inflammatory cells and relevant immune checkpoint inhibitors are the focus of active investigation. The most numerous tumor-infiltrating inflammatory cells are tumor-associated macrophages (TAMs) and CD3+ T cells. Studies have shown that patients with GISTs that harbor increased numbers of CD3+ T cells have better outcomes...
February 10, 2017: Cancer Gene Therapy
https://www.readbyqxmd.com/read/28186087/baculovirus-directly-activates-murine-nk-cells-via-tlr9
#11
T Moriyama, T Suzuki, M O Chang, M Kitajima, H Takaku
The importance of natural killer (NK) cells in innate immune responses against tumors or viral infections enhances the appeal of NK cell-based immunotherapeutic approaches. We have recently reported that baculovirus (BV)-infected dendritic cells (DCs; BV-DCs) induce antitumor immunity against established tumors in mice. These antitumor effects were CD8(+) T-cell and NK cell dependent; however, they were found to be CD4(+) T-cell independent. In this study, we investigated the involvement of Toll-like receptor 9 (TLR9) in the process of BV recognition by NK cells...
February 10, 2017: Cancer Gene Therapy
https://www.readbyqxmd.com/read/28161224/cox-2-inhibitor-prevents-tumor-induced-down-regulation-of-classical-dc-lineage-specific-transcription-factor-zbtb46-resulting-in-immunocompetent-dc-and-decreased-tumor-burden
#12
Vipul K Pandey, Prayag J Amin, Bhavani S Shankar
The interaction between the immune and tumor cells in the microenvironment is an important factor deciding the progression of cancer. Though many of the soluble mediators in the microenvironment that mediate immunosuppression are known, the mechanism by which the tumor affects the distal progenitors is not known. We report that the tumor derived prostanoids down regulated classical dendritic cells DC (cDC) lineage specific transcription factor Zbtb46 in the progenitor cells which affects its differentiation...
February 1, 2017: Immunology Letters
https://www.readbyqxmd.com/read/28159747/nk-cell-recruitment-is-necessary-for-eradication-of-peritoneal-carcinomatosis-with-an-il12-expressing-maraba-virus-cellular-vaccine
#13
Almohanad A Alkayyal, Lee-Hwa Tai, Michael A Kennedy, Christiano Tanese de Souza, Jiqing Zhang, Charles Lefebvre, Shalini Sahi, Abhirami A Ananth, Ahmad Bakur Mahmoud, Andrew P Makrigiannis, Greg O Cron, Blair Macdonald, E Celia Marginean, David F Stojdl, John C Bell, Rebecca C Auer
Despite improvements in chemotherapy and radical surgical debulking, peritoneal carcinomatosis (PC) remains among the most common causes of death from abdominal cancers. Immunotherapies have been effective for selected solid malignancies, but their potential in PC has been little explored. Here, we report that intraperitoneal injection of an infected cell vaccine (ICV), consisting of autologous tumor cells infected ex vivo with an oncolytic Maraba MG1 virus expressing IL12, promotes the migration of activated natural killer (NK) cells to the peritoneal cavity in response to the secretion of IFNγ-induced protein-10 (IP-10) from dendritic cells...
February 3, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28153581/delivery-of-tlr7-agonist-to-monocytes-and-dendritic-cells-by-dcir-targeted-liposomes-induces-robust-production-of-anti-cancer-cytokines
#14
Thomas C B Klauber, Janne M Laursen, Daniel Zucker, Susanne Brix, Simon S Jensen, Thomas L Andresen
: Tumor immune escape is today recognized as an important cancer hallmark and is therefore a major focus area in cancer therapy. Monocytes and dendritic cells (DCs), which are central to creating a robust anti-tumor immune response and establishing an anti-tumorigenic microenvironment, are directly targeted by the tumor escape mechanisms to develop immunosuppressive phenotypes. Providing activated monocytes and DCs to the tumor tissue is therefore an attractive way to break the tumor-derived immune suppression and reinstate cancer immune surveillance...
January 30, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/28143792/2003-2013-a-valuable-study-autologous-tumor-lysate-pulsed-dendritic-cell-immunotherapy-with-cytokine-induced-killer-cells-improves-survival-in-stage-iv-breast-cancer
#15
Mao Lin, Shuzhen Liang, Feng Jiang, Jiongyuan Xu, Weibing Zhu, Wei Qian, Yong Hu, Zhanchun Zhou, Jibing Chen, Lizhi Niu, Kecheng Xu, Youyong Lv
Dendritic cells (DCs) and cytokine-induced killer (CIK) cells have both shown activity as immunotherapy in some malignancies. Our aim was to prospective assess the effect of this immunotherapy in patients with stage IV breast cancer. Between Aug 2003 and Dec 2013, we collected 368 patients who met inclusion criteria and divided into immunotherapy group (treatment group: 188 patients) and chemotherapy group (control group: 180 patients). DCs were prepared from the mononuclear cells isolated from patients in the treatment group using IL-2/GM-CSF and were loaded with tumour antigens; CIK cells were prepared by incubating peripheral blood lymphocytes with IL-2, IFN-γ, and CD3 antibodies...
January 29, 2017: Immunology Letters
https://www.readbyqxmd.com/read/28138787/the-development-of-dendritic-cell-vaccine-based-immunotherapies-for-glioblastoma
#16
REVIEW
David A Reardon, Duane A Mitchell
In this review, we focus on the biologic advantages of dendritic cell-based vaccinations as a therapeutic strategy for cancer as well as preclinical and emerging clinical data associated with such approaches for glioblastoma patients.
January 30, 2017: Seminars in Immunopathology
https://www.readbyqxmd.com/read/28137885/cgas-is-essential-for-the-antitumor-effect-of-immune-checkpoint-blockade
#17
Hua Wang, Shuiqing Hu, Xiang Chen, Heping Shi, Chuo Chen, Lijun Sun, Zhijian J Chen
cGMP-AMP (cGAMP) synthase (cGAS) is a cytosolic DNA sensor that activates innate immune responses. cGAS catalyzes the synthesis of cGAMP, which functions as a second messenger that binds and activates the adaptor protein STING to induce type I interferons (IFNs) and other immune modulatory molecules. Here we show that cGAS is indispensable for the antitumor effect of immune checkpoint blockade in mice. Wild-type, but not cGAS-deficient, mice exhibited slower growth of B16 melanomas in response to a PD-L1 antibody treatment...
January 30, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28129580/immunotherapy-with-dendritic-cells-modified-with-tumor-associated-antigen-gene-demonstrates-enhanced-antitumor-effect-against-lung-cancer
#18
Tao Jiang, Xiao Chen, Wei Zhou, Guoxin Fan, Peilin Zhao, Shengxiang Ren, Caicun Zhou, Jun Zhang
BACKGROUND: Immunotherapy using dendritic cell (DC) vaccine has the potential to overcome the bottleneck of cancer therapy. METHODS: We engineered Lewis lung cancer cells (LLCs) and bone marrow-derived DCs to express tumor-associated antigen (TAA) ovalbumin (OVA) via lentiviral vector plasmid encoding OVA gene. We then tested the antitumor effect of modified DCs both in vitro and in vivo. RESULTS: The results demonstrated that in vitro modified DCs could dramatically enhance T-cell proliferation (P<...
January 24, 2017: Translational Oncology
https://www.readbyqxmd.com/read/28116870/multicomponent-injectable-hydrogels-for-antigen-specific-tolerogenic-immune-modulation
#19
Catia S Verbeke, Susana Gordo, David A Schubert, Sarah A Lewin, Rajiv M Desai, Jessica Dobbins, Kai W Wucherpfennig, David J Mooney
Biomaterial scaffolds that enrich and modulate immune cells in situ can form the basis for potent immunotherapies to elicit immunity or reëstablish tolerance. Here, the authors explore the potential of an injectable, porous hydrogel to induce a regulatory T cell (Treg) response by delivering a peptide antigen to dendritic cells in a noninflammatory context. Two methods are described for delivering the BDC peptide from pore-forming alginate gels in the nonobese diabetic mouse model of type 1 diabetes: encapsulation in poly(lactide-co-glycolide) (PLG) microparticles, or direct conjugation to the alginate polymer...
January 24, 2017: Advanced Healthcare Materials
https://www.readbyqxmd.com/read/28111040/-immunotherapy-in-brain-tumors
#20
Emilie De Carli, Matthieu Delion, Audrey Rousseau
Diffuse gliomas represent the most common primary central nervous system (CNS) tumors in adults and children alike. Glioblastoma is the most frequent and malignant form of diffuse glioma with a median overall survival of 15 months despite aggressive treatments. New therapeutic approaches are needed to prolong survival in this always fatal disease. The CNS has been considered for a long time as an immune privileged organ, in part because of the existence of the blood-brain barrier. Nonetheless, immunotherapy is a novel approach in the therapeutic management of glioma patients, which has shown promising results in several clinical trials, especially in the adult population...
January 19, 2017: Annales de Pathologie
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