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Dendritic Cell Therapy

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https://www.readbyqxmd.com/read/28932640/co-delivery-of-the-nkt-agonist-%C3%AE-galactosylceramide-and-tumor-antigens-to-cross-priming-dendritic-cells-breaks-tolerance-to-self-antigens-and-promotes-antitumor-responses
#1
Reem Ghinnagow, Julie De Meester, Luis Javier Cruz, Caroline Aspord, Stéphanie Corgnac, Elodie Macho-Fernandez, Daphnée Soulard, Josette Fontaine, Laurence Chaperot, Julie Charles, Fabrice Soncin, Fathia Mami-Chouaib, Joel Plumas, Christelle Faveeuw, François Trottein
Vaccines designed to abrogate the tolerance of tumor self-antigens and amplify cytotoxic CD8(+) T cells (CTLs) have promise for the treatment of cancer. Type I natural killer (NKT) cells have attracted considerable interest in the cancer therapy field. In the current study, we have exploited the unique ability of NKT cells to serve as T-helper cells to license dendritic cells (DCs) for cross priming with the aim to generate efficient CTL antitumor responses. To this end, we designed a nanoparticle-based vaccine to target cross-priming DCs via the Clec9a endocytic pathway...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28932627/addition-of-anti-estrogen-therapy-to-anti-her2-dendritic-cell-vaccination-improves-regional-nodal-immune-response-and-pathologic-complete-response-rate-in-patients-with-er-pos-her2-pos-early-breast-cancer
#2
Lea Lowenfeld, Salman Zaheer, Crystal Oechsle, Megan Fracol, Jashodeep Datta, Shuwen Xu, Elizabeth Fitzpatrick, Robert E Roses, Carla S Fisher, Elizabeth S McDonald, Paul J Zhang, Angela DeMichele, Rosemarie Mick, Gary K Koski, Brian J Czerniecki
HER2-directed therapies are less effective in patients with ER(pos) compared to ER(neg) breast cancer, possibly reflecting bidirectional activation between HER2 and estrogen signaling pathways. We investigated dual blockade using anti-HER2 vaccination and anti-estrogen therapy in HER2(pos)/ER(pos) early breast cancer patients. In pre-clinical studies of HER2(pos) breast cancer cell lines, ER(pos) cells were partially resistant to CD4(+) Th1 cytokine-induced metabolic suppression compared with ER(neg) cells...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28928941/computational-design-of-molecular-motors-as-nanocircuits-in-leishmaniasis
#3
Dipali Kosey, Shailza Singh
Cutaneous leishmaniasis is the most common form of lesihmaniasis, caused by Leishmania major and is spread by the bite of a sandfly .This species infects the macrophages and dendritic cells Due to multi-drug resistance, there is a need for a new therapeutic technique. Recently, a novel molecular motor of Leishmania, Myosin XXI, was classified and characterized. In addition, the drug resistance in this organism has been linked with the overexpression of ABC transporters. Systems biology aims to study the simulation and modeling of natural biological systems whereas synthetic biology deals with building novel and artificial biological parts and devices  Together they have contributed enormously to drug discovery, vaccine design and development, infectious disease detection and diagnostics...
2017: F1000Research
https://www.readbyqxmd.com/read/28926357/first-in-human-treatment-with-a-dendritic-cell-targeting-lentiviral-vector-expressing-ny-eso-1-lv305-induces-deep-durable-response-in-refractory-metastatic-synovial-sarcoma-patient
#4
Seth M Pollack, Hailing Lu, Sacha Gnjatic, Neeta Somaiah, Ryan B O'Malley, Robin L Jones, Frank J Hsu, Jan Ter Meulen
Effective induction of antitumor T cells is a pivotal goal of cancer immunotherapy. To this end, lentiviral vectors (LV) are uniquely poised to directly prime CD8 T-cell responses via transduction of dendritic cells in vivo and have shown promise as active cancer therapeutics in preclinical tumor models. However, until now, significant barriers related to production and regulation have prevented their widespread use in the clinic. We developed LV305, a dendritic cell-targeting, integration-deficient, replication incompetent LV from the ZVex platform, encoding the full-length cancer-testis antigen NY-ESO-1...
September 18, 2017: Journal of Immunotherapy
https://www.readbyqxmd.com/read/28924177/loss-of-mapk-activated-protein-kinase-2-enables-potent-dendritic-cell-driven-anti-tumour-t-cell-response
#5
Klara Soukup, Angela Halfmann, Barbara Dillinger, Fiona Poyer, Katharina Martin, Bernadette Blauensteiner, Maximilian Kauer, Mario Kuttke, Gernot Schabbauer, Alexander M Dohnal
Maintaining dendritic cells (DC) in a state of dysfunction represents a key mechanism by which tumour cells evade recognition and elimination by the immune system. Limited knowledge about the intracellular mediators of DC dysfunction restricts success of therapies aimed at reactivating a DC-driven anti-tumour immune response. Using a cell type-specific murine knock-out model, we have identified MAPK-activated protein kinase 2 (MK2) as a major guardian of a suppressive DC phenotype in the melanoma tumour microenvironment...
September 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28923424/depletion-of-regulatory-t-cells-by-anti-icos-antibody-enhances-anti-tumor-immunity-of-tumor-cell-vaccine-in-prostate-cancer
#6
Lijun Mo, Qianmei Chen, Xinji Zhang, Xiaojun Shi, Lili Wei, Dianpeng Zheng, Hongwei Li, Jimin Gao, Jinlong Li, Zhiming Hu
ICOS(+)Treg cells exert important immunosuppressive effects in tumor immunity. We adopt a combination approach of ICOS(+)Treg cells depletion with tumor cell vaccine to evaluate anti-tumor immunity in mouse prostate cancer model. Streptavidin (SA)-mGM-CSF surface-modified RM-1 cells were prepared as the vaccine and the mouse subcutaneous prostate tumor model was used to evaluate the immunity. Tumor growth, flow cytometry, immunohistochemistry, immunofluorescence and enzyme linked immunosorbent assay (ELISA) were performed to evaluate the therapeutic effects...
September 15, 2017: Vaccine
https://www.readbyqxmd.com/read/28919780/the-role-and-significance-of-vegfr2-regulatory-t-cells-in-tumor-immunity
#7
REVIEW
Panrong Zhu, Chenxi Hu, Kaiyuan Hui, Xiaodong Jiang
Tumor development is closely related to angiogenesis, and VEGFR2 plays an important role in tumor angiogenesis. It is broadly expressed in the blood vessels, especially in the microvessels of tumor tissues. Furthermore, VEGFR2 is detected on the surface of the cell membrane in various immune cells, such as dendritic cells, macrophages, and regulatory T cells (Tregs). Tregs, which are one of the key negative regulatory factors in tumor immune microenvironments, show high-level expression of VEGFR2 which participates in the regulation of immunosuppressive function...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28919508/pro-inflammatory-chitosan-poly-%C3%AE-glutamic-acid-nanoparticles-modulate-human-antigen-presenting-cells-phenotype-and-revert-their-pro-invasive-capacity
#8
Flávia Castro, Marta L Pinto, Andreia M Silva, Catarina L Pereira, Graciosa Q Teixeira, Maria Gomez-Lazaro, Susana G Santos, Mário A Barbosa, Raquel M Gonçalves, Maria J Oliveira
Anticancer immune responses depend on efficient presentation of tumor antigens and co-stimulatory signals provided by antigen-presenting cells (APCs). However, it is described that immature dendritic cells (DCs) and macrophages at the tumor site may have an immunosuppressive profile, which limits the activity of effector T cells and supports tumor progression. Therapeutic targeting of these innate immune cells, either aiming at their elimination or re-polarization towards an immunostimulatory profile, has been pointed as an attractive approach to control tumor progression...
September 14, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/28918908/macrophage-biology-plays-a-central-role-during-ionizing-radiation-elicited-tumor-response
#9
REVIEW
Qiuji Wu, Awatef Allouch, Isabelle Martins, Nazanine Modjtahedi, Eric Deutsch, Jean-Luc Perfettini
Radiation therapy is one of the major therapeutic modalities for most solid tumors. The anti-tumor effect of radiation therapy consists of the direct tumor cell killing, as well as the modulation of tumor microenvironment and the activation of immune response against tumors. Radiation therapy has been shown to promote immunogenic cells death, activate dendritic cells and enhance tumor antigen presentation and anti-tumor T cell activation. Radiation therapy also programs innate immune cells such as macrophages that leads to either radiosensitization or radioresistance, according to different tumors and different radiation regimen studied...
August 2017: Biomedical Journal
https://www.readbyqxmd.com/read/28916248/breast-cancer-vaccines-delivered-by-dendritic-cell-targeted-lentivectors-induce-potent-antitumor-immune-responses-and-protect-mice-from-mammary-tumor-growth
#10
Paul D Bryson, Xiaolu Han, Norman Truong, Pin Wang
Breast cancer immunotherapy is a potent treatment option, with antibody therapies such as trastuzumab increasing 2-year survival rates by 50%. However, active immunotherapy through vaccination has generally been clinically ineffective. One potential means of improving vaccine therapy is by delivering breast cancer antigens to dendritic cells (DCs) for enhanced antigen presentation. To accomplish this in vivo, we pseudotyped lentiviral vector (LV) vaccines with a modified Sindbis Virus glycoprotein so that they could deliver genes encoding the breast cancer antigen alpha-lactalbumin (Lalba) or erb-b2 receptor tyrosine kinase 2 (ERBB2 or HER2) directly to resident DCs...
September 12, 2017: Vaccine
https://www.readbyqxmd.com/read/28915900/a-randomized-phase-ii-study-to-assess-the-effect-of-adjuvant-immunotherapy-using-%C3%AE-galcer-pulsed-dendritic-cells-in-the-patients-with-completely-resected-stage-ii-iiia-non-small-cell-lung-cancer-study-protocol-for-a-randomized-controlled-trial
#11
Hideo Saka, Chiyoe Kitagawa, Yukito Ichinose, Mitsuhiro Takenoyama, Hidenori Ibata, Tatsuo Kato, Koji Takami, Motohiro Yamashita, Tadashi Maeda, Sadanori Takeo, Hitoshi Ueda, Kan Okabayashi, Seiji Nagashima, Tadayuki Oka, Hidenori Kouso, Seiichi Fukuyama, Kentaro Yoshimoto, Mototsugu Shimokawa, Akiko M Saito, Suminobu Ito
BACKGROUND: As the toxicity associated with the α-GalCer-pulsed dendritic cell (DC) therapy could be considered to be negligible, its addition to postoperative adjuvant chemotherapy would be expected to greatly improve the therapeutic effect, and could result in prolonged survival. The aim of the present study is to compare the therapeutic efficacy of alpha-galactosylceramide-pulsed DC therapy in patients who have undergone a complete resection of stage II-IIIA non-small-cell lung cancer (NSCLC) followed by postoperative adjuvant therapy with cisplatin plus vinorelbine, to that in patients who did not receive additional treatment (surgical resection plus postoperative adjuvant chemotherapy only)...
September 15, 2017: Trials
https://www.readbyqxmd.com/read/28912828/dendritic-immunotherapy-improvement-for-an-optimal-control-murine-model
#12
J C Rangel-Reyes, J C Chimal-Eguía, E Castillo-Montiel
Therapeutic protocols in immunotherapy are usually proposed following the intuition and experience of the therapist. In order to deduce such protocols mathematical modeling, optimal control and simulations are used instead of the therapist's experience. Clinical efficacy of dendritic cell (DC) vaccines to cancer treatment is still unclear, since dendritic cells face several obstacles in the host environment, such as immunosuppression and poor transference to the lymph nodes reducing the vaccine effect. In view of that, we have created a mathematical murine model to measure the effects of dendritic cell injections admitting such obstacles...
2017: Computational and Mathematical Methods in Medicine
https://www.readbyqxmd.com/read/28910387/epstein-barr-virus-latent-membrane-protein-1-enhances-dendritic-cell-therapy-lymph-node-migration-activation-and-il-12-secretion
#13
James M Termini, Sachin Gupta, Francesca N Raffa, Elizabeth Guirado, Margaret A Fischl, Liguo Niu, Saravana Kanagavelu, Geoffrey W Stone
Dendritic cells (DC) are a promising cell type for cancer vaccines due to their high immunostimulatory capacity. However, improper maturation of DC prior to treatment may account for the limited efficacy of DC vaccine clinical trials. Latent Membrane Protein-1 (LMP1) of Epstein-Barr virus was examined for its ability to mature and activate DC as a gene-based molecular adjuvant for DC vaccines. DC were transduced with an adenovirus 5 vector (Ad5) expressing LMP1 under the control of a Tet-inducible promoter...
2017: PloS One
https://www.readbyqxmd.com/read/28906324/pediatric-blastic-plasmacytoid-dendritic-cell-neoplasm-a-systematic-literature-review
#14
Marie Jeong-Min Kim, Ahmed Nasr, Bilaal Kabir, Joseph de Nanassy, Ken Tang, Danielle Menzies-Toman, Donna Johnston, Dina El Demellawy
Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare aggressive hematologic malignancy characterized by frequent skin involvement that most commonly affects older patients. BPDCN is known to have a poor prognosis. Our objective was to assess if outcome and disease prognosis were independently influenced by age when evaluated with clinical presentation, sex, and treatment regimens. We conducted a systematic review to identify BPDCN cases, to compare pediatric BPDCN cases with adult cases. A total of 125 publications were identified detailing 356 cases...
September 12, 2017: Journal of Pediatric Hematology/oncology
https://www.readbyqxmd.com/read/28905887/an-efficient-non-viral-dendritic-vector-for-gene-delivery-in-tissue-engineering
#15
D P Walsh, A Heise, F J O'Brien, S-A Cryan
Recent developments within the field of tissue engineering (TE) have shown that biomaterial scaffold systems can be augmented via the incorporation of gene therapeutics. The objective of this study was to assess the potential of the activated polyamidoamine dendrimer (dPAMAM) transfection reagent (Superfect(TM)) as a gene delivery system to mesenchymal stem cells (MSCs) in both monolayer and 3D culture on collagen based scaffolds. dPAMAM-pDNA polyplexes at a mass ratio (M:R) 10:1 (dPAMAM : pDNA) (1 ug pDNA) were capable of facilitating prolonged reporter gene expression in monolayer MSCs which was superior to that facilitated using polyethylenimine (PEI)-pDNA polyplexes (2 ug pDNA)...
September 14, 2017: Gene Therapy
https://www.readbyqxmd.com/read/28904191/the-dose-of-retroviral-infection-determines-the-induction-of-anti-viral-nk-cell-responses
#16
Elisabeth Littwitz-Salomon, Simone Schimmer, Ulf Dittmer
Natural killer (NK) cells are part of the innate immune system and recognize virus-infected cells as well as tumor cells. Conflicting data about the beneficial or even detrimental role of NK cells in different infectious diseases were described. While the type of pathogen strongly influences NK cell functionality, less is known about how the infection dose influences the quality of a NK cell response against retroviruses. Here we used the well-established Friend retrovirus (FV) mouse model to investigate the impact of virus dose on the induction of anti-viral NK cell functions...
September 13, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28901740/inhibiting-metastasis-and-preventing-tumor-relapse-by-triggering-host-immunity-with-tumor-targeted-photodynamic-therapy-using-photosensitizer-loaded-functional-nanographenes
#17
Xinhe Yu, Duo Gao, Liquan Gao, Jianhao Lai, Chenran Zhang, Yang Zhao, Lijun Zhong, Bing Jia, Fan Wang, Xiaoyuan Chen, Zhaofei Liu
Effective cancer therapy depends not only on destroying the primary tumor but also on conditioning the host immune system to recognize and eliminate residual tumor cells and prevent metastasis. In this study, a tumor integrin αvβ6-targeting peptide (the HK peptide)-functionalized graphene oxide (GO) was coated with a photosensitizer (HPPH). The resulting GO conjugate, GO(HPPH)-PEG-HK, was investigated whether it could destroy primary tumors and boost host antitumor immunity. We found that GO(HPPH)-PEG-HK exhibited significantly higher tumor uptake than GO(HPPH)-PEG and HPPH...
September 18, 2017: ACS Nano
https://www.readbyqxmd.com/read/28899494/intranasal-co-administration-of-1-8-cineole-with-influenza-vaccine-provide-cross-protection-against-influenza-virus-infection
#18
Yun Li, Yu-Ling Xu, Yan-Ni Lai, Shang-Hui Liao, Ni Liu, Pei-Ping Xu
BACKGROUND: Vaccination is the most efficient means for protection against influenza. However, the various vaccines have low efficacy to protect against pandemic strains because of antigenic drift and recombination of influenza virus. Adjuvant therapy is one of the attempts to improve influenza vaccine effective cross-protection against influenza virus infection. Our previous study confirmed that 1,8-cineole inhibits the NF-κB, reduces pro-inflammatory cytokines, and relieves the pathological changes of viral pneumonia in mice infected with influenza virus...
October 15, 2017: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
https://www.readbyqxmd.com/read/28894045/neopterin-as-a-marker-of-cellular-immunological-response
#19
Łukasz Michalak, Magdalena Bulska, Karolina Strząbała, Piotr Szcześniak
Neopterin is a pyrazino-pyrimidine compound that belongs to the pteridine group. It is known to be a biochemical marker associated with cell-mediated immunity. It is produced by human monocytes/macrophages and dendritic cells from guanosine triphosphate (GTP) upon stimulation with interferon gamma (IFNγ), which is released by activated limphocytes Th. Neopterin is a very important clinic parameter, though the physiological role has not been exactly definited thus far. The level of neopterin reflects the stage of activation of the cellular immune system, which is important in the pathogenesis and progression of various diseases...
August 24, 2017: Postȩpy Higieny i Medycyny Doświadczalnej
https://www.readbyqxmd.com/read/28892752/graphene-quantum-dots-suppress-proinflammatory-t-cell-responses-via-autophagy-dependent-induction-of-tolerogenic-dendritic-cells
#20
Sergej Tomić, Kristina Janjetović, Dušan Mihajlović, Marina Milenković, Tamara Kravić-Stevović, Zoran Marković, Biljana Todorović-Marković, Zdenko Spitalsky, Matej Micusik, Dragana Vučević, Miodrag Čolić, Vladimir Trajković
Graphene quantum dots (GQD) are atom-thick nanodimensional carbon sheets with excellent physico-chemical and biological properties, making them attractive for application in theranostics. However, their immunoregulatory properties are insufficiently investigated, especially in human primary immune cells. We found that non-toxic doses of GQD inhibit the production of proinflammatory and T helper (Th)1 cytokines, and augment the production of anti-inflammatory and Th2 cytokines by human peripheral blood mononuclear cells...
August 29, 2017: Biomaterials
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