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Dendritic cell vaccine

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https://www.readbyqxmd.com/read/28640587/silica-nanoparticle-as-a-lymph-node-targeting-platform-for-vaccine-delivery
#1
Myunggi An, Meng Li, Jingchao Xi, Haipeng Liu
Nanoparticles have emerged as the platform of choice to improve the efficacy and safety of subunit vaccines. A major challenge underlying the use of nanomaterials in vaccines lies in the particle designs that can efficiently target and activate the antigen-presenting cells, especially dendritic cells. Here we show a toll-like receptor 9 (TLR-9) agonist and antigen co-loaded, silica nanoparticles (SiNPs) are able to accumulate in antigen presenting cells in the draining lymph nodes after injection. Vaccine loaded SiNPs led to dramatically enhanced induction of antigen-specific B and T cell responses as compared to soluble vaccines, which in turn drove a protective antitumoral immunity in a murine tumor model...
June 22, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28636997/an-optimized-hmgb1-expressed-by-recombinant-rabies-virus-enhances-immunogenicity-through-activation-of-dendritic-cells-in-mice
#2
Zhao Wang, Qian Liang, Yajing Zhang, Jie Yang, Mingming Li, Kunlun Wang, Min Cui, Huanchun Chen, Zhen F Fu, Ling Zhao, Ming Zhou
Rabies remains an important public health threat, killing approximately 59,000 people worldwide annually, most of which are from the developing countries of Africa and Asia where dog rabies are endemic. Therefore, developing an affordable and efficacious vaccine for dog-mediated rabies control is needful in these countries. Our previous studies indicated that over-expression of granulocyte-macrophage colony stimulating factor (GM-CSF) or macrophage inflammatory protein-1 (MIP-1α or CCL3) by recombinant rabies virus (rRABV) could enhance the immunogenicity by activating dendritic cells (DCs)...
June 5, 2017: Oncotarget
https://www.readbyqxmd.com/read/28634588/antitumor-effect-of-kml-b-treated-dendritic-cells-via-induction-of-lymphocyte-activation
#3
Jong-Jin Kim, Yun-Ho Hwang, Kyung-Yun Kang, Sung-Ju Lee, Jong-Bae Kim, Jina Choi, Sung-Tae Yee
Lectins are carbohydrate-binding proteins with various biological activities, such as antitumor and immunomodulatory effects. Although lectins have various biological activities, they are still limited by cytotoxicity in normal cells. To overcome this problem, we used the noncytotoxic part of Korean mistletoe lectin B-chain (KML-B) to induce maturation of dendritic cells (DCs). A previous study reported that KML-B induces DC maturation by triggering TLR-4, including expression of costimulatory molecules (CD40, CD80, and CD86), MHC II, and secretion of cytokines in DCs...
2017: Journal of Immunology Research
https://www.readbyqxmd.com/read/28633645/generation-of-populations-of-antigen-specific-cytotoxic-t-cells-using-dcs-transfected-with-dna-construct-encoding-her2-neu-tumor-antigen-epitopes
#4
Maria Kuznetsova, Julia Lopatnikova, Julia Khantakova, Rinat Maksyutov, Amir Maksyutov, Sergey Sennikov
BACKGROUND: Recent fundamental and clinical studies have confirmed the effectiveness of utilizing the potential of the immune system to remove tumor cells disseminated in a patient's body. Cytotoxic T lymphocytes (CTLs) are considered the main effectors in cell-mediated antitumor immunity. Approaches based on antigen presentation to CTLs by dendritic cells (DCs) are currently being intensively studied, because DCs are more efficient in tumor antigen presentation to T cells through their initiation of strong specific antitumor immune responses than other types of antigen-presenting cells...
June 20, 2017: BMC Immunology
https://www.readbyqxmd.com/read/28630093/dendritic-cell-sensing-of-hydrophobic-di-and-triacylated-lipopeptides-self-assembled-within-synthetic-virus-like-particles
#5
Rajni Sharma, Arin Ghasparian, John A Robinson, Kenneth C McCullough
Dendritic cells (DCs) play critical roles in developing immune defenses. One important aspect is interaction with pathogen-associated molecular patterns (PAMPs)/danger-associated molecular patterns, including di- and triacylated lipopeptides. Isolated or synthetic lipopeptides are potent vaccine adjuvants, interacting with cell surface TLR2 heterodimers. In contrast, deep embedment within bacteria cell walls would impair lipopeptide interaction with cell surface TLR2, requiring degradation for PAMP recognition...
June 19, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28630078/what-are-the-primary-limitations-in-b-cell-affinity-maturation-and-how-much-affinity-maturation-can-we-drive-with-vaccination-a-role-for-antibody-feedback
#6
Kai-Michael Toellner, Daniel M-Y Sze, Yang Zhang
We discuss the impact of antibody feedback on affinity maturation of B cells. Competition from epitope-specific antibodies produced earlier during the immune response leads to immune complex formation, which is essential for transport and deposition of antigen onto follicular dendritic cells (FDCs). It also reduces the concentration of free epitopes into the μm to nm range, which is essential for B-cell receptors (BCRs) to sense affinity-dependent changes in binding capacity. Antibody feedback may also induce epitope spreading, leading to a broader selection of epitopes recognized by newly emerging B-cell clones...
June 19, 2017: Cold Spring Harbor Perspectives in Biology
https://www.readbyqxmd.com/read/28628011/-criteria-for-selection-of-tumor-cells-and-prospects-for-specific-immunotherapy-for-bladder-cancer
#7
T Slavyanskaya, S -Salnikova, R Sepiashvili
Specific antitumor immunotherapy with autologous dendritic cell vaccines is one of the new approaches of modern medicine. For activation of dendritic cells highly immunogenic antigens are used, however optimal antigens in case of bladder cancer (BC) are still not researched. Cancer-testis antigens (CTA) are the most promising target in the context of creation of antitumor vaccines, because they are distinguished by pronounced immunogenicity, they are detected in different types of tumors and have limited pattern of expression in healthy tissues of grown-up organism...
May 2017: Georgian Medical News
https://www.readbyqxmd.com/read/28628010/-the-main-stages-of-the-preparation-of-viable-tumor-cells-of-bladder-cancer-from-isolation-of-the-tumor-material-till-cryopreservation-of-cell-lines
#8
T Slavyanskaya, S -Salnikova
The development of personalized autologous dendritic cell anti-tumor vaccines (PDPW) against bladder cancer (BC) is a relevant issue that covers many aspects required for its standardization. The article presents personal experimental studies related to development of optimal conditions of transportation of biological material; temperature and temporary modes for the storage of the samples; the materials about the optimal method of disaggregation of the biomaterial; there has been shown a comparative analysis of different methods of tumor disaggregation; the selection of nutritious growth mediums and growth factors for urothelial carcinoma cells (UCC), the conditions of cryopreservation of tumor cells for maximum UCC viability, potentially suitable for creating PDPW against BC...
May 2017: Georgian Medical News
https://www.readbyqxmd.com/read/28624137/effect-of-tlr-ligands-co-encapsulated-with-multiepitopic-antigen-in-nanoliposomes-targeted-to-human-dcs-via-fc-receptor-for-cancer-vaccines
#9
Felix Rueda, Christina Eich, Begoña Cordobilla, Pere Domingo, Gerardo Acosta, Fernando Albericio, Luis J Cruz, Joan C Domingo
Nanoliposomes (NLs) hold promise as new highly specific nanomedicine for anti-tumor vaccines, since they could be targeted to specific receptors on dendritic cell (DC) to induce maturation and activation and increase the anti-tumor immune response. Here we studied a NLs formulation targeted or not to FcR (the receptor for the IgG Fc fragment) for the treatment of androgen-responsive prostate cancer. Luteinizing-hormone-releasing hormone (LHRH) peptide (B- and T-cell epitopes), in tandem with a tetanus toxoid T-helper epitope (830-844 region) and several TLR (Toll-Like Receptor) ligands as adjuvants were co-encapsulated...
June 10, 2017: Immunobiology
https://www.readbyqxmd.com/read/28619138/newcastle-disease-virus-like-particles-induce-dc-maturation-through-tlr4-nf-%C3%AE%C2%BAb-pathway-and-facilitate-dc-migration-by-ccr7-ccl19-ccl21-axis
#10
Jing Qian, Xiaohong Xu, Jiaxin Ding, Renfu Yin, Yixue Sun, Cong Xue, Jianzhong Wang, Chan Ding, Shengqing Yu, Xiufan Liu, Shunlin Hu, Chunfeng Wang, Yanlong Cong, Zhuang Ding
Newcastle disease virus-like particles (NDV VLPs) are a potential candidate vaccine, as shown by eliciting specific immune response against NDV in mice and chickens. Activation of dendritic cells (DCs) is critical to initiate immune response. However, the mechanism of how NDV VLPs induce DC maturation and migration remains elusive. In this study, we found that NDV VLPs are efficient in DC activation by up-regulating surface MHC II and costimulatory molecules, and proinflammatory cytokines through the TLR4/NF-κB pathway...
May 2017: Veterinary Microbiology
https://www.readbyqxmd.com/read/28617554/the-study-on-specific-umbilical-blood-dc-vaccine-for-beige-nude-mice-loaded-human-colorectal-carcinoma-to-induce-anti-tumor-immunity
#11
Z-X Fu, J-S Han, F Liu, Z-L Zhao, D-B Li, L Shi, J-T Dong, Y Zhou, J-H Cai
OBJECTIVE: This study is to observe the immunosuppression of CD137L transfected umbilical blood Dcs (Dendritic cell) vaccine to tumor development of SCID/ Beige nude mice. MATERIALS AND METHODS: Samples of umbilical blood in the childbirth pregnant women were collected by density gradient centrifugation. Umbilical cord blood dendritic cells (Dcs) were transfected by specific CD137L via LipofectamineTM method and cells were harvested. Meanwhile, the peripheral blood of volunteers was collected to isolate Dcs, the Dcs were cultured for 5 days and hatched with SW-1116 cells antigen...
May 2017: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/28612840/toll-like-receptor-3-in-nasal-cd103-dendritic-cells-is-involved-in-immunoglobulin-a-production
#12
H Takaki, S Kure, H Oshiumi, Y Sakoda, T Suzuki, A Ainai, H Hasegawa, M Matsumoto, T Seya
Intranasal inoculation with influenza hemagglutinin subunit with polyinosine-polycytidylic (polyI:C), a synthetic analog for double-stranded RNA, enhances production of vaccine-specific immunoglobulin (Ig) A, which is superior to IgG in prophylactic immunity. The mechanism whereby polyI:C skews to IgA production in the nasal-associated lymph tissue (NALT) was investigated in mouse models. Nasally instilled polyI:C was endocytosed into CD103(+) dendritic cells (DCs) and induced T-cell activation, including interferon (IFN)-γ production...
June 14, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/28610825/integrating-next-generation-dendritic-cell-vaccines-into-the-current-cancer-immunotherapy-landscape
#13
REVIEW
Abhishek D Garg, Pierre G Coulie, Benoit J Van den Eynde, Patrizia Agostinis
Cancer immunotherapy is experiencing a renaissance spearheaded by immune checkpoint inhibitors (ICIs). This has spurred interest in 'upgrading' existing immunotherapies that previously experienced only sporadic success, such as dendritic cells (DCs) vaccines. In this review, we discuss the major molecular, immunological, and clinical determinants of existing first- and second-generation DC vaccines. We also outline the future trends for next-generation DC vaccines and describe their major hallmarks and prerequisites necessary for high anticancer efficacy...
June 10, 2017: Trends in Immunology
https://www.readbyqxmd.com/read/28608115/phase-i-trial-of-antigen-targeted-autologous-dendritic-cell-based-vaccine-with-in-vivo-activation-of-inducible-cd40-for-advanced-prostate-cancer
#14
Guru Sonpavde, John D McMannis, Yu Bai, Mamatha R Seethammagari, Joan M C Bull, Victoria Hawkins, Theresa K Dancsak, Natasha Lapteva, Jonathan M Levitt, Annemarie Moseley, David M Spencer, Kevin M Slawin
This phase I trial reports the safety and activity of BPX101, a second-generation antigen-targeted autologous antigen presenting cell (APC) vaccine in men with metastatic castration-resistant prostate cancer (mCRPC). To manufacture BPX101, APCs collected in a single leukapheresis were transduced with adenoviral vector Ad5f35 encoding inducible human (ih)-CD40, followed by incubation with protein PA001, which contains the extracellular domain of human prostate-specific membrane antigen. The ih-CD40 represents a modified chimeric version of the dendritic cell (DC) co-stimulatory molecule, CD40, which responds to a bioinert membrane-permeable activating dimerizer drug, rimiducid (AP1903), permitting temporally controlled, lymphoid-localized, DC-specific activation...
June 12, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28603864/ediii-denv3-nanospheres-drive-immature-dendritic-cells-into-a-mature-phenotype-in-an-in-vitro-model
#15
Nattika Nantachit, Panya Sunintaboon, Sukathida Ubol
Domain III of E protein of DENV is one of the targets for vaccine development. Unfortunately, this protein-based platform has generally low immunogenicity. To circumvent this problem, we investigated the use of an adjuvant-nanoparticle delivery system to facilitate immunogenicity of soluble DENV-EDIII protein. One of the key features of this delivery system is its ability to simultaneously deliver antigens and exert adjuvanticity to specialized immune cells. In this study, we generated N-trimethyl chitosan (TMC) nanoparticles (NPs) to be used as adjuvant and carrier for the soluble E-domain III of dengue virus serotype 3 (sEDIII-D3)...
June 12, 2017: Microbiology and Immunology
https://www.readbyqxmd.com/read/28601925/enhanced-stimulation-of-human-tumor-specific-t-cells-by-dendritic-cells-matured-in-the-presence-of-interferon-%C3%AE-and-multiple-toll-like-receptor-agonists
#16
Tanja Lövgren, Dhifaf Sarhan, Iva Truxová, Bhavesh Choudhary, Roeltje Maas, Jeroen Melief, Maria Nyström, Ulrika Edbäck, Renee Vermeij, Gina Scurti, Michael Nishimura, Giuseppe Masucci, Alex Karlsson-Parra, Andreas Lundqvist, Lars Adamson, Rolf Kiessling
Dendritic cell (DC) vaccines have been demonstrated to elicit immunological responses in numerous cancer immunotherapy trials. However, long-lasting clinical effects are infrequent. We therefore sought to establish a protocol to generate DC with greater immunostimulatory capacity. Immature DC were generated from healthy donor monocytes by culturing in the presence of IL-4 and GM-CSF and were further differentiated into mature DC by the addition of cocktails containing different cytokines and toll-like receptor (TLR) agonists...
June 10, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28601924/tgf-%C3%AE-1-silenced-leukemia-cell-derived-exosomes-target-dendritic-cells-to-induce-potent-anti-leukemic-immunity-in-a-mouse-model
#17
Fang Huang, Jiangbo Wan, Siguo Hao, Xiaohui Deng, Linjun Chen, Liyuan Ma
Tumor-derived exosomes (TEX) can induce a specific antitumor immune response and have been developed as a promising tumor vaccine. Despite promising preclinical data, TEX exhibit relatively low efficacy and limited clinical benefit in clinical trials. In the present study, we investigated whether exosomes from the TGF-β1 silenced L1210 cells (LEXTGF-β1si) can enhance the efficacy of DC-based vaccines. We silenced TGF-β1 in L1210 cells with a lentiviral shRNA vector and prepared the LEXTGF-β1si. It was shown that LEXTGF-β1si can significantly decrease TGF-β1 expression of dendritic cells (DC) and effectively promote their maturation and immune function...
June 10, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28594355/comparing-proteolytic-fingerprints-of-antigen-presenting-cells-during-allergen-processing
#18
Heidi Hofer, Tamara Weidinger, Peter Briza, Claudia Asam, Martin Wolf, Teresa E Twaroch, Frank Stolz, Angela Neubauer, Elfriede Dall, Peter Hammerl, Alain Jacquet, Michael Wallner
Endolysosomal processing has a critical influence on immunogenicity as well as immune polarization of protein antigens. In industrialized countries, allergies affect around 25% of the population. For the rational design of protein-based allergy therapeutics for immunotherapy, a good knowledge of T cell-reactive regions on allergens is required. Thus, we sought to analyze endolysosomal degradation patterns of inhalant allergens. Four major allergens from ragweed, birch, as well as house dust mites were produced as recombinant proteins...
June 8, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28592561/vaccine-priming-is-restricted-to-draining-lymph-nodes-and-controlled-by-adjuvant-mediated-antigen-uptake
#19
Frank Liang, Gustaf Lindgren, Kerrie J Sandgren, Elizabeth A Thompson, Joseph R Francica, Anja Seubert, Ennio De Gregorio, Susan Barnett, Derek T O'Hagan, Nancy J Sullivan, Richard A Koup, Robert A Seder, Karin Loré
The innate immune mechanisms by which adjuvants enhance the potency and protection of vaccine-induced adaptive immunity are largely unknown. We introduce a model to delineate the steps of how adjuvant-driven innate immune activation leads to priming of vaccine responses using rhesus macaques. Fluorescently labeled HIV-1 envelope glycoprotein (Env) was administered together with the conventional aluminum salt (alum) adjuvant. This was compared to Env given with alum with preabsorbed Toll-like receptor 7 (TLR7) ligand (alum-TLR7) or the emulsion MF59 because they show superiority over alum for qualitatively and quantitatively improved vaccine responses...
June 7, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28589429/influence-of-ovarian-cancer-type-i-and-type-ii-microenvironment-on-the-phenotype-and-function-of-monocyte-derived-dendritic-cells
#20
J Surówka, I Wertel, K Okła, W Bednarek, R Tarkowski, J Kotarski
PURPOSE: The aim of this study was to evaluate the influence of ovarian cancer cell lysates isolated from type I or type II ovarian cancer (OC) on the phenotype of monocyte-derived dendritic cells (Mo-DCs) and the cytokine profile. We also determined whether the Mo-DCs and tumor microenvironment, reflected by peritoneal fluid (PF) from type I or II ovarian cancer, could promote regulatory T cell (Tregs) differentiation from naive CD4(+) lymphocytes in vitro. RESULTS: Our results show a significant role of the ovarian cancer microenvironment reflected by PF from type I or II OC in the inhibition of the DC differentiation process...
June 6, 2017: Clinical & Translational Oncology
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