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DC vaccine

Junya Kitadani, Toshiyasu Ojima, Hiromitsu Iwamoto, Hirotaka Tabata, Mikihito Nakamori, Masaki Nakamura, Keiji Hayata, Masahiro Katsuda, Masayasu Miyajima, Hiroki Yamaue
Clinical application of dendritic cell (DC) vaccine therapy is hindered by the need for a large quantity of DCs generated from peripheral blood monocytes of the patient. We investigated whether genetically modified human induced pluripotent stem cell (iPSC)-derived dendritic cells (hiPSDCs) expressing carcinoembryonic antigen (CEA) could induce CEA-specific cytotoxic T cells in a human model and whether genetically modified mouse iPSDCs (miPSDCs) expressing CEA showed an actual antitumor effect using a CEA transgenic mouse model...
March 15, 2018: Scientific Reports
Karen L Wozniak
The fungal pathogens Cryptococcus neoformans and Cryptococcus gattii can cause life-threatening infections in immune compromised and immune competent hosts. These pathogens enter the host via inhalation, and respiratory tract innate immune cells such as dendritic cells (DCs) are one of the first host cells they encounter. The interactions between Cryptococcus and innate immune cells play a critical role in the progression of disease in the host. This review will focus specifically on the interactions between Cryptococcus and dendritic cells (DCs), including recognition/processing by DCs, effects of immune mediators on DC recruitment and activity, and the potential for DC vaccination against cryptococcosis...
March 15, 2018: Journal of Fungi (Basel, Switzerland)
Liam V Brown, Eamonn A Gaffney, Jonathan Wagg, Mark C Coles
Tumour immunotherapy is dependent upon activation and expansion of tumour-targetting immune cells, known as cytotoxic T-lymphocytes (CTLs). Cancer vaccines developed in the past have had limited success and the mechanisms resulting in failure are not well characterized. To elucidate these mechanisms, we developed a human-parametrized, in silico , agent-based model of vaccination-driven CTL activation within a clinical short-peptide vaccination context. The simulations predict a sharp transition in the probability of CTL activation, which occurs with variation in the separation rate (or off-rate) of tumour-specific immune response-inducing peptides (cognate antigen) from the major histocompatibility class I (MHC-I) receptors of dendritic cells (DCs) originally at the vaccination site...
March 2018: Journal of the Royal Society, Interface
Felix S Lichtenegger, Maurine Rothe, Frauke M Schnorfeil, Katrin Deiser, Christina Krupka, Christian Augsberger, Miriam Schlüter, Julia Neitz, Marion Subklewe
Immune checkpoint inhibition has been shown to successfully reactivate endogenous T cell responses directed against tumor-associated antigens, resulting in significantly prolonged overall survival in patients with various tumor entities. For malignancies with low endogenous immune responses, this approach has not shown a clear clinical benefit so far. Therapeutic vaccination, particularly dendritic cell (DC) vaccination, is a strategy to induce T cell responses. Interaction of DCs and T cells is dependent on receptor-ligand interactions of various immune checkpoints...
2018: Frontiers in Immunology
Nicole Zimara, Menberework Chanyalew, Abraham Aseffa, Ger van Zandbergen, Bernd Lepenies, Maximilian Schmid, Richard Weiss, Anne Rascle, Anja Kathrin Wege, Jonathan Jantsch, Valentin Schatz, Gordon D Brown, Uwe Ritter
Resistant mouse strains mount a protective T cell-mediated immune response upon infection with Leishmania (L.) parasites. Healing correlates with a T helper (Th) cell-type 1 response characterized by a pronounced IFN-γ production, while susceptibility is associated with an IL-4-dependent Th2-type response. It has been shown that dermal dendritic cells are crucial for inducing protective Th1-mediated immunity. Additionally, there is growing evidence that C-type lectin receptor (CLR)-mediated signaling is involved in directing adaptive immunity against pathogens...
2018: Frontiers in Immunology
Chalathan Saengruengrit, Patcharee Ritprajak, Supason Wanichwecharungruang, Apoorva Sharma, Georgeta Salvan, Dietrich R T Zahn, Numpon Insin
Superparamagnetic iron oxide nanoparticles (SPIONs) have received much attention in drug and biomolecule delivery systems. Here, we report a delivery system using the combination of a magnetic field and the relatively biocompatible composite particles of poly(lactic-co-glycolic acid) and SPIONs (SPION-PLGA particles) for protein delivery to bone-marrow derived primary dendritic cells (BM-DCs). SPIONs with the diameter of ∼10 nm were synthesized via thermal decomposition of iron(III) oleate. The SPIONs and bovine serum albumin (BSA) were encapsulated in PLGA particles of two different diameters, 300 and 500 nm...
March 3, 2018: Journal of Colloid and Interface Science
Yujuan Chen, Fengjiao Yuan, Xian Jiang, Qing Lv, Na Luo, Changyang Gong, Chunting Wang, Li Yang, Gu He
Recently, tumor immunotherapy has achieved great progress in the treatment of hematological and solid neoplasms. The DC vaccines, KLH-conjugated vaccines or glycosylated peptide vaccines can efficiently induce immune responses against tumors. In the current study, we have discovered cholesteryl PADRE-EGFRvIII epitope-conjugated lipopeptide self-assembled micelles as a potential self-adjuvant vaccine against cutaneous melanoma. The lipopeptide vaccines were synthesized using a standard solid phase peptide synthesis method, and these vaccines could elicit both a humoral and a cellular immune response to EGFRvIII positive melanoma cells...
March 12, 2018: Biomaterials Science
Tsukasa Seya, Yohei Takeda, Ken Takashima, Sumito Yoshida, Masahiro Azuma, Misako Matsumoto
The immune system eliminates advanced cancer when treated with programmed cell death protein-1 (PD-1) or its ligand (PD-L1) blockade, but PD-1 therapy is effective in only ∼20% of patients with solid cancer. The PD-1 antibody mainly acts on the effector phase of cytotoxic T lymphocytes (CTLs) in tumors but induces no activation of the priming phase of antigen-presenting dendritic cells (DCs). It is reasonable that both DC-priming and PD-1/L1 blocking are mandatory for efficient CTL-mediated tumor cytolysis...
2018: Proceedings of the Japan Academy. Series B, Physical and Biological Sciences
Sally A F El-Sahrigy, Azza M O Abdel Rahman, Dalia Y Samaha, Nesrine A Mohamed, Sally M Saber, Hala A Talkhan, Ghada A Ismail, Essam M Ibraheem, Emad M Riad
INTRODUCTION: Tuberculosis (TB) remains a huge worldwide burden, despite extensive vaccination coverage with the Bacillus Calmette-Guérin (BCG), the only vaccine available against this disease, indicating that BCG-driven immunity is inadequate to protect the human population against TB. This underscore the critical necessitate to develop an improved TB vaccine, based on a better understanding of host-pathogen interactions and immune responses during mycobacterial infection. AIM OF THE WORK: To examine whether the exogenous addition of IFN-β could improve dendritic cell (DC) response to Mycobacterium bovis (M...
March 6, 2018: Journal of Immunological Methods
Shinya Yamamoto, Kazuhiko Matsuo, Daisuke Nagakubo, Shintaro Higashiyama, Keiji Nishiwaki, Naoki Oiso, Akira Kawada, Osamu Yoshie, Takashi Nakayama
CCR4 is a major chemokine receptor expressed by Treg cells that downregulate immune responses. Here, we investigated the role of CCR4-mediated Treg cell recruitment in antigen-specific immune responses. CCR4-deficient mice immunized intramuscularly with ovalbumin (OVA) showed enhanced OVA-specific IgG responses. Furthermore, intramuscular administration of OVA induced the expression of MDC/CCL22, a ligand for CCR4, in macrophages of the muscle tissues, and enhanced the recruitment of CCR4+ Treg cells in wild-type mice, whereas this recruitment of Treg cells was severely impaired in CCR4-deficient mice...
February 8, 2018: Journal of Pharmacological Sciences
Giulia Franzoni, Simon P Graham, Giovanna Sanna, Pierpaolo Angioi, Mariangela S Fiori, Antonio Anfossi, Massimo Amadori, Silvia Dei Giudici, Annalisa Oggiano
African swine fever (ASF) is a devastating disease for which there is no vaccine. The ASF virus (ASFV) can infect dendritic cell (DC), but despite the critical role these cells play in induction of adaptive immunity, few studies investigated their response to ASFV infection. We characterized the in vitro interactions of porcine monocyte-derived DCs (moDC) with a virulent (22653/14), a low virulent (NH/P68) and an avirulent (BA71V) ASFV strain. At a high multiplicity of infection (MOI = 1), all three strains infected immature moDC...
March 2018: Veterinary Microbiology
Hatem Soliman, Fatema Khambati, Hyo S Han, Roohi Ismail-Khan, Marilyn M Bui, Daniel M Sullivan, Scott Antonia
Background: Indoleamine 2, 3-dioxygenase is an enzyme that causes immunosuppression in tumors. Indoximod inhibits the indoleamine 2, 3-dioxygenase pathway and enhances immunologic responses to dendritic cell (DC) vaccines preclinically. Adenovirus p53 (Ad.p53) is used to generate DC vaccines against p53. A phase-1/2 trial of indoximod with Ad.p53-DC vaccine was conducted. Materials and Methods: The phase-1 study combined 7 indoximod dose levels with < 6 Ad.p53-DC vaccinations every 2 weeks...
February 9, 2018: Oncotarget
Zineb Lakhrif, Alexis Moreau, Bruno Hérault, Anne Di-Tommaso, Matthieu Juste, Nathalie Moiré, Isabelle Dimier-Poisson, Marie-Noëlle Mévélec, Nicolas Aubrey
Toxoplasmosis is a major public health problem and the development of a human vaccine is of high priority. Efficient vaccination against Toxoplasma gondii requires both a mucosal and systemic Th1 immune response. Moreover, dendritic cells play a critical role in orchestrating the innate immune functions and driving specific adaptive immunity to T. gondii . In this study, we explore an original vaccination strategy that combines administration via mucosal and systemic routes of fusion proteins able to target the major T...
2018: Frontiers in Immunology
Najmeh Khosravianfar, Jamshid Hadjati, Afshin Namdar, Roobina Boghozian, Morteza Hafezi, Mahboubeh Ashourpour, Nasim Kheshtchin, Mahsa Banitalebi, Reza Mirzaei, Seyed Alireza Razavi
Myeloid-derived suppressor cells (MDSCs) are capable of suppressing the immune response. 5-Fluorouracil (5-FU) compared to other chemotherapy drugs have shown considerable decreases in the number of MDSCs without visible effects on T, B and natural killer cells, as well as dendritic cells (DCs). DC-based vaccines considered to be appropriate candidates for cancer immunotherapy. However, due to the presence of various factors like MDSCs in tumor microenvironment, DC vaccine cannot effectively perform its function...
February 2018: Iranian Journal of Allergy, Asthma, and Immunology
Bhushan Dharmadhikari, Emily Nickles, Zulkarnain Harfuddin, Nur Diana Binte Ishak, Qun Zeng, Antonio Bertoletti, Herbert Schwarz
Therapeutic tumor vaccination based on dendritic cells (DC) is safe; however, its efficacy is low. Among the reasons for only a subset of patients benefitting from DC-based immunotherapy is an insufficient potency of in vitro generated classical DCs (cDCs), made by treating monocytes with GM-CSF + IL-4 + maturation factors. Recent studies demonstrated that CD137L (4-1BBL, TNFSF9) signaling differentiates human monocytes to a highly potent novel type of DC (CD137L-DCs) which have an inflammatory phenotype and are closely related to in vivo DCs...
March 5, 2018: Cancer Immunology, Immunotherapy: CII
Xingyu Hou, Xinpeng Jiang, Yanping Jiang, Lijie Tang, Yigang Xu, Xinyuan Qiao, Liu Min, Cui Wen, Guangpeng Ma, Yijing Li
Porcine epidemic diarrhea (PED) is a highly contagious disease in newborn piglets. In our previous study, a genetically engineered Lactobacillus casei oral vaccine ( pPG-COE-DCpep/L393 ) expressing a dendritic cell (DC)-targeting peptide fused with porcine epidemic diarrhea virus (PEDV) COE antigen was developed. This vaccine induced significant levels of anti-PEDV specific IgG and IgA antibody responses in mice, indicating a potential strategy against PEDV infection. In this study, pPG-COE-DCpep/L393 was used for oral vaccination of newborn piglets against PEDV...
March 1, 2018: Viruses
Hyunjoon Kim, Lin Niu, Peter Larson, Tamara A Kucaba, Katherine A Murphy, Britnie R James, David M Ferguson, Thomas S Griffith, Jayanth Panyam
Cytotoxic T lymphocytes (CTLs) play a major role in cancer immunotherapy because of their ability to directly kill tumor cells and secrete tumor suppressive cytokines. Anticancer vaccines aim to provoke tumor-specific CTL responses, which require activation of antigen presenting cells (APCs) including dendritic cells (DCs) and macrophages. Therefore, a potent immunostimulatory adjuvant capable of activating APCs is an essential component of anticancer vaccines. In this study, we introduce novel TLR 7/8 bi-specific agonists that significantly enhance cytokine secretion compared to TLR7 mono-selective compounds...
February 17, 2018: Biomaterials
Mark O Hardin, Timothy J Vreeland, Guy T Clifton, Diane F Hale, Garth S Herbert, Julia M Greene, Doreen O Jackson, John E Berry, Pauline Nichols, Sook Yin, Xianzhong Yu, Thomas E Wagner, George E Peoples
AIM:  We developed a novel approach to efficiently deliver autologous tumor antigens to the cytoplasm of dendritic cells (DC) using yeast cell wall particles (YCWP). MATERIALS AND METHODS:  Loading of YCWP, leakage of protein from loaded YCWP and cytoplasmic delivery of YCWP content was assessed using fluorescent-tagged experiments. Spectrophotometric analysis compared the epitope-specific T-cell responses following antigen presentation via YCWP versus exogenous loading...
April 2018: Immunotherapy
Megan C Roberts, Taylor Murphy, Jennifer L Moss, Christopher W Wheldon, Wayne Psek
OBJECTIVES: To examine how combinations of state policies, rather than single policies, are related to uptake of human papillomavirus (HPV) vaccine. METHODS: Using publicly available records and the literature, we characterized policies for each US state and Washington, DC, in 2015 (n = 51), including (1) Medicaid expansion, (2) policies permitting HPV vaccination in pharmacies, (3) school-entry requirements, (4) classroom sex education mandates, and (5) parental education mandates...
February 22, 2018: American Journal of Public Health
Barbara Montico, Annunziata Nigro, Vincenzo Casolaro, Jessica Dal Col
Immunogenic apoptosis, or more appropriately called immunogenic cell death (ICD), is a recently described form of apoptosis induced by a specific set of chemotherapeutic drugs or by physical therapeutic modalities, such as ionizing irradiation and photodynamic therapy. The peculiar characteristic of ICD is the ability to favor recognition and elimination of dying tumor cells by phagocytes in association with the release of pro-inflammatory molecules (such as cytokines and high-mobility group box-1). While in vitro and animal models pointed to ICD as one of the molecular mechanisms mediating the clinical efficacy of some anticancer agents, it is hard to clearly demonstrate its contribution in cancer patients...
February 16, 2018: International Journal of Molecular Sciences
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