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https://www.readbyqxmd.com/read/28638734/severe-but-not-mild-heat-shock-treatment-induces-immunogenic-cell-death-in-cancer-cells
#1
Irena Adkins, Lenka Sadilkova, Nada Hradilova, Jakub Tomala, Marek Kovar, Radek Spisek
The mechanisms of immunogenicity underlying mild heat-shock (mHS) treatment < 42°C of tumor cells are largely attributed to the action of heat-shock proteins; however, little is known about the immunogenicity of tumor cells undergoing severe cytotoxic heat-shock treatment (sHS > 43°C). Here, we found that sHS, but not mHS (42°C), induces immunogenic cell death in human cancer cell lines as defined by the induction of ER stress response and ROS generation, cell surface exposure of calreticulin, HSP70 and HSP90, decrease of cell surface CD47, release of ATP and HMGB1...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28638480/mouse-ip-10-gene-delivered-by-folate-modified-chitosan-nanoparticles-and-dendritic-tumor-cells-fusion-vaccine-effectively-inhibit-the-growth-of-hepatocellular-carcinoma-in-mice
#2
Zixi Hu, Jiaojiao Chen, Sufang Zhou, Nuo Yang, Siliang Duan, Zhenghua Zhang, Jing Su, Jian He, Zhiyong Zhang, Xiaoling Lu, Yongxiang Zhao
Dendritic cells (DC) and tumor cell fusion vaccine (DC/tumor cell fusion vaccine) is considered an effective approach in cancer biotherapy. However, its therapeutic effects in early clinical trials have been suboptimal partially due to the immunosuppressive tumor environment. In this study, we used nanoparticles of folate (FA)-modified chitosan, a non-viral vector capable of targeting tumor cells with high expression of FA receptors. FA-chitosan nanoparticles were used as biological carriers for the expression plasmid of the mouse interferon-induced protein-10 (mIP-10) gene, a potent chemoattractant for cytotoxic T cells...
2017: Theranostics
https://www.readbyqxmd.com/read/28637876/monocyte-derived-dendritic-cells-with-silenced-pd-1-ligands-and-transpresenting-interleukin-15-stimulate-strong-tumor-reactive-t-cell-expansion
#3
Johan Mj Van den Bergh, Evelien Ljm Smits, Zwi N Berneman, Tim Ja Hutten, Hans De Reu, Viggo Fi Van Tendeloo, Harry Dolstra, Eva Lion, Willemijn Hobo
Although allogeneic stem cell transplantation (allo-SCT) can elicit graft-versus-tumor (GVT) immunity, patients often relapse due to residual tumor cells. As essential orchestrators of the immune system, vaccination with dendritic cells (DCs) is an appealing strategy to boost the GVT-response. Nevertheless, durable clinical responses after DC vaccination are still limited, stressing the need to improve current DC vaccines. Aiming to empower DC potency, we engineered monocyte-derived DCs to deprive them of ligands for the immune checkpoint regulated by programmed death 1 (PD-1)...
June 21, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28634886/subcortical-brain-atrophy-in-gulf-war-illness
#4
Peka Christova, Lisa M James, Brian E Engdahl, Scott M Lewis, Adam F Carpenter, Apostolos P Georgopoulos
Gulf War Illness (GWI) is a multisystem disorder that has affected a substantial number of veterans who served in the 1990-1991 Gulf War. The brain is prominently affected, as manifested by the presence of neurological, cognitive and mood symptoms. Although brain dysfunction in GWI has been well documented (EBioMedicine 12:127-32, 2016), abnormalities in brain structure have been debated. Here we report a substantial (~10%) subcortical brain atrophy in GWI comprising mainly the brainstem, cerebellum and thalamus, and, to a lesser extent, basal ganglia, amygdala and diencephalon...
June 20, 2017: Experimental Brain Research. Experimentelle Hirnforschung. Expérimentation Cérébrale
https://www.readbyqxmd.com/read/28634588/antitumor-effect-of-kml-b-treated-dendritic-cells-via-induction-of-lymphocyte-activation
#5
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/28630093/dendritic-cell-sensing-of-hydrophobic-di-and-triacylated-lipopeptides-self-assembled-within-synthetic-virus-like-particles
#6
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/28624137/effect-of-tlr-ligands-co-encapsulated-with-multiepitopic-antigen-in-nanoliposomes-targeted-to-human-dcs-via-fc-receptor-for-cancer-vaccines
#7
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/28621316/combination-of-p53-dc-vaccine-and-rad-p53-gene-therapy-induced-ctls-cytotoxic-against-p53-deleted-human-prostate-cancer-cells-in-vitro
#8
H Saito, K Kitagawa, T Yoneda, Y Fukui, M Fujsawa, D Bautista, T Shirakawa
Recently, the US FDA approved sipuleucel-T, which is composed of autologous DCs stimulated with a recombinant fusion protein of prostatic acid phosphatase (PAP) and granulocyte-macrophage colony-stimulating factor (GM-CSF), as the first immunotherapeutic agent for metastatic castration resistant prostate cancer (mCRPC). However, sipuleucel-T demonstrated only modest efficacy in mCPRC patients. Researchers are now investigating the potential of p53 protein as a tumor-associated antigen (TAA) loaded in DC-based cancer vaccine...
June 16, 2017: Cancer Gene Therapy
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
#9
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
#10
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/28610825/integrating-next-generation-dendritic-cell-vaccines-into-the-current-cancer-immunotherapy-landscape
#11
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
#12
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/28606814/does-cost-effectiveness-of-influenza-vaccine-choice-vary-across-the-u-s-an-agent-based-modeling-study
#13
Jay V DePasse, Mary Patricia Nowalk, Kenneth J Smith, Jonathan M Raviotta, Eunha Shim, Richard K Zimmerman, Shawn T Brown
BACKGROUND: In a prior agent-based modeling study, offering a choice of influenza vaccine type was shown to be cost-effective when the simulated population represented the large, Washington DC metropolitan area. This study calculated the public health impact and cost-effectiveness of the same four strategies: No Choice, Pediatric Choice, Adult Choice, or Choice for Both Age Groups in five United States (U.S.) counties selected to represent extremes in population age distribution. METHODS: The choice offered was either inactivated influenza vaccine delivered intramuscularly with a needle (IIV-IM) or an age-appropriate needle-sparing vaccine, specifically, the nasal spray (LAIV) or intradermal (IIV-ID) delivery system...
June 9, 2017: Vaccine
https://www.readbyqxmd.com/read/28603864/ediii-denv3-nanospheres-drive-immature-dendritic-cells-into-a-mature-phenotype-in-an-in-vitro-model
#14
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
#15
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
#16
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/28589429/influence-of-ovarian-cancer-type-i-and-type-ii-microenvironment-on-the-phenotype-and-function-of-monocyte-derived-dendritic-cells
#17
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
https://www.readbyqxmd.com/read/28586072/treatment-of-colon-cancer-cells-with-5-fluorouracil-can-improve-the-effectiveness-of-rna-transfected-antitumor-dendritic-cell-vaccine
#18
Carolina V De Almeida, Jofer A Zamame, Graziela G Romagnoli, Cecilia P Rodrigues, Marianna B Magalhães, Amedeo Amedei, Ramon Kaneno
Non-cytotoxic concentrations of selected chemotherapeutic agents amplify the antigen presentation capacity of dendritic cells (DCs) and are able to increase the immunogenicity of the colon cancer cell lineage HCT‑116, as previously demonstrated by our group. Since this functional alteration was associated with changes in gene expression, we aimed to evaluate whether transcriptional changes of tumor cells can be transferred to DCs, increasing their ability to induce a specific antitumor response. Therefore, HCT‑116 cells were treated with two different concentrations of 5-fluorouracil (5-FU), and their total RNA was transfected into human monocyte-derived DC, which function was evaluated through their ability to stimulate the proliferation of normal allogeneic T lymphocytes (MLR), and to generate cytolytic T cells...
June 1, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28585000/immunization-with-antigen-pulsed-dendritic-cells-against-highly-virulent-cryptococcus-gattii-infection-analysis-of-cytokine-producing-t-cells
#19
Keigo Ueno, Makoto Urai, Shogo Takatsuka, Masahiro Abe, Yoshitsugu Miyazaki, Yuki Kinjo
Cryptococcosis caused by highly virulent Cryptococcus gattii (Hv-Cg) is an emerging infectious disease that affects immunocompetent individuals. The Hv-Cg outbreak began in 1999, but the mechanisms responsible for its hyper-virulence as well as protective immunity against Hv-Cg infection remain to be elucidated. To better understand the protective immunity against Hv-Cg infection, we developed a novel immunization method using antigen-pulsed dendritic cells (DCs). We constructed a capsule-deficient Cg strain (∆cap60) and used it as a vaccine antigen...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28581468/a-phase-i-ii-minor-histocompatibility-antigen-loaded-dendritic-cell-vaccination-trial-to-safely-improve-the-efficacy-of-donor-lymphocyte-infusions-in-myeloma
#20
L E Franssen, M W H Roeven, W Hobo, R Doorn, R Oostvogels, J H F Falkenburg, N W van de Donk, M G D Kester, H Fredrix, K Westinga, I Slaper-Cortenbach, E Spierings, M J Kersten, H Dolstra, T Mutis, N Schaap, H M Lokhorst
Allogeneic stem cell transplantation (allo-SCT) with or without donor lymphocyte infusions (DLI) is the only curative option for several hematological malignancies. Unfortunately, allo-SCT is often associated with GvHD, and patients often relapse. We therefore aim to improve the graft-versus-tumor effect, without increasing the risk of GvHD, by targeting hematopoietic lineage-restricted and tumor-associated minor histocompatibility antigens using peptide-loaded dendritic cell (DC) vaccinations. In the present multicenter study, we report the feasibility, safety and efficacy of this concept...
June 5, 2017: Bone Marrow Transplantation
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