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https://www.readbyqxmd.com/read/29164490/immunotherapy-with-interferon-%C3%AE-induced-dendritic-cells-for-chronic-hcv-infection-the-results-of-pilot-clinical-trial
#1
Elena Chernykh, Olga Leplina, Ekaterina Oleynik, Marina Tikhonova, Tamara Tyrinova, Natalia Starostina, Alexandr Ostanin
The key role of T cells in hepatitis C virus (HCV) elimination and the ability of dendritic cells (DCs) to induce antiviral T cell responses suggest that DC vaccines could be a promising approach in the treatment of chronic HCV infection. The aim of our study was to evaluate, whether immunotherapy with DCs is safe and elicits anti-HCV T cell responses. Ten patients with HCV (genotype 1) were vaccinated with monocyte-derived DCs, generated in the presence of IFN-α (IFN-DCs) and pulsed with recombinant HCV Core and NS3 proteins...
November 21, 2017: Immunologic Research
https://www.readbyqxmd.com/read/29157976/loading-dendritic-cells-with-gold-nanoparticles-gnps-bearing-hiv-peptides-and-mannosides-enhance-hiv-specific-t-cell-responses
#2
Núria Climent, Isabel García, Marco Marradi, Fabrizio Chiodo, Laia Miralles, María José Maleno, José María Gatell, Felipe García, Soledad Penadés, Montserrat Plana
Gold nanoparticles (GNPs) decorated with glycans ameliorate dendritic cells (DC) uptake, antigen-presentation and T-cells cross-talk, which are important aspects in vaccine design. GNPs allow for high antigen loading, DC targeting, lack of toxicity and are straightforward prepared and easy to handle. The present study aimed to assess the capacity of DC to process and present HIV-1-peptides loaded onto GNPs bearing high-mannoside-type oligosaccharides (P1@HM) to autologous T-cells from HIV-1 patients. The results showed that P1@HM increased HIV-specific CD4(+) and CD8(+) T-cell proliferation and induced highly functional cytokine secretion compared with HIV-peptides alone...
November 17, 2017: Nanomedicine: Nanotechnology, Biology, and Medicine
https://www.readbyqxmd.com/read/29151181/screening-hcv-genotype-specific-epitope-peptides-based-on-conserved-sequence-analysis-and-b-cell-epitope-prediction-in-hcv-e2-region
#3
Rui Hua, Xiaoyu Jiang, Lingxia Qi, Shanshan Guan, Ziyu Kuai, Yongbo Qiao, Yan Xu, Xin Gong, Yuhua Shi, Wei Kong, Junqi Niu, Hao Zhang, Yaming Shan
The high mutation rate of the hepatitis C virus (HCV) genome increases the genotype diversity and renders the detection of the virus more difficult. Therefore, prediction and assessment of highly conserved and strongly antigenic epitope polypeptide sequences have become a focus of current research. The E2 region is the target binding region of neutralizing antibodies. HCV genomics, especially the high mutation rate of E2 region sequence, makes its genotyping more and more diverse, and the detection of HCV and genotype is becoming more and more strict...
November 18, 2017: Immunologic Research
https://www.readbyqxmd.com/read/29147614/exploiting-a-new-strategy-to-induce-immunogenic-cell-death-to-improve-dendritic-cell-based-vaccines-for-lymphoma-immunotherapy
#4
B Montico, C Lapenta, M Ravo, D Martorelli, E Muraro, B Zeng, E Comaro, M Spada, S Donati, S M Santini, R Tarallo, G Giurato, F Rizzo, A Weisz, F Belardelli, R Dolcetti, J Dal Col
Although promising, the clinical benefit provided by dendritic cell (DC)-based vaccines is still limited and the choice of the optimal antigen formulation is still an unresolved issue. We have developed a new DC-based vaccination protocol for aggressive and/or refractory lymphomas which combines the unique features of interferon-conditioned DC (IFN-DC) with highly immunogenic tumor cell lysates (TCL) obtained from lymphoma cells undergoing immunogenic cell death. We show that treatment of mantle cell lymphoma (MCL) and diffuse large B-cell lymphoma (DLBCL) cell lines with 9-cis-retinoic acid and IFNα (RA/IFNα) induces early membrane exposure of Calreticulin, HSP70 and 90 together with CD47 down-regulation and enhanced HMGB1 secretion...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/29146881/beta-adrenergic-signaling-impairs-anti-tumor-cd8-t-cell-responses-to-b-cell-lymphoma-immunotherapy
#5
Michael D Nissen, Erica K Sloan, Stephen R Mattarollo
Beta-adrenergic receptor (betaAR) signaling regulates many physiological processes, including immune system responses. There is growing evidence also for betaAR-induced modulation of cancer growth and metastasis. In the Eu-myc mouse model of B-cell lymphoma, we investigated the effects of chronically elevated betaAR signaling on lymphoma progression and anti-tumor immunity, as well as the impact on cancer immunotherapy. Chronic treatment with the non-selective beta-agonist isoprenaline promoted lymphoma development in a manner dependent on signaling within the hematopoietic compartment...
November 16, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/29143114/cancer-vaccine-strategies-translation-from-mice-to-human-clinical-trials
#6
REVIEW
Jay A Berzofsky, Masaki Terabe, Jane B Trepel, Ira Pastan, David F Stroncek, John C Morris, Lauren V Wood
We translated two cancer vaccine strategies from mice into human clinical trials. (1) In preclinical studies on TARP, an antigen expressed in most prostate cancers, we mapped epitopes presented by HLA-A*0201, modified them to increase affinity and immunogenicity in HLA transgenic mice, and induced human T cells that killed human cancer cells ("epitope enhancement"). In a clinical trial, HLA-A2(+) prostate cancer patients with PSA biochemical recurrence (Stage D0) were vaccinated with two peptides either in Montanide-ISA51 or on autologous dendritic cells (DCs)...
November 15, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/29134568/%C3%AE-2-adrenergic-stimulation-of-dendritic-cells-favors-il-10-secretion-by-cd4-t-cells
#7
Julie Hervé, Karine Haurogné, Elodie Bacou, Sylvie Pogu, Marie Allard, Grégoire Mignot, Jean-Marie Bach, Blandine Lieubeau
Adrenergic receptor agonists and antagonists are extensively used as drugs in medicine for a broad spectrum of indications. We examined the consequences of β2-adrenergic stimulation of murine dendritic cells (DCs) on CD4(+) T cell activation. We demonstrated in vitro that treatment of LPS-matured DCs with the β2-agonist salbutamol reduced their ability to trigger OT-II T cell proliferation specific for ovalbumin antigen. Salbutamol also induced a decrease in MHC class II molecule expression by DC through Gi protein activation...
November 14, 2017: Immunologic Research
https://www.readbyqxmd.com/read/29130994/enhancement-of-anti-leukemia-immunity-by-leukemia-derived-exosomes-via-downregulation-of-tgf-%C3%AE-1-expression
#8
Fang Huang, Jiangbo Wan, Weiwei Hu, Siguo Hao
BACKGROUND/AIMS: Minimal residual leukemia cells (MRLs) are difficult to eradicate through traditional treatment and therefore remain to be a major threat to the long-term survival of leukemia patients. Tumor-derived exosomes (TEXs), which carry tumor associated antigens (TAA), may be a potential cell-free tumor vaccine for the specific eradication of MRLs. However, TEXs are intended to be less immunogenic due to exosomal TGF-β1. To further optimize the efficacy of TEX-based vaccines, we investigated whether exosomes from TGF-β1 silenced leukemia cells (LEXTGF-β1si) had an increased potential to induce a specific antitumor effect compared with non-modified exosomes...
November 9, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29119112/expression-and-immunogenicity-of-two-recombinant-fusion-proteins-comprising-foot-and-mouth-disease-virus-structural-protein-vp1-and-dc-sign-binding-glycoproteins
#9
Xinsheng Liu, Jianliang Lv, Yuzhen Fang, Peng Zhou, Yanzhen Lu, Li Pan, Zhongwang Zhang, Junwu Ma, Yongguang Zhang, Yonglu Wang
Improving vaccine immunogenicity by targeting antigens to dendritic cells has recently emerged as a new design strategy in vaccine development. In this study, the VP1 gene of foot-and-mouth disease virus (FMDV) serotype A was fused with the gene encoding human immunodeficiency virus (HIV) membrane glycoprotein gp120 or C2-V3 domain of hepatitis C virus (HCV) envelope glycoprotein E2, both of which are DC-SIGN-binding glycoproteins. After codon optimization, the VP1 protein and the two recombinant VP1-gp120 and VP1-E2 fusion proteins were expressed in Sf9 insect cells using the insect cell-baculovirus expression system...
2017: BioMed Research International
https://www.readbyqxmd.com/read/29119057/dendritic-cells-based-immunotherapy
#10
REVIEW
Na Shang, Matteo Figini, Junjie Shangguan, Bin Wang, Chong Sun, Liang Pan, Quanhong Ma, Zhuoli Zhang
Dendritic cells (DCs) are the most potent antigen-presenting cells, and tumor antigen-loaded DCs (DC-vaccines) can activate tumor-specific cytotoxic T lymphocytes (CTLs) in lymphatic tissues. DC vaccination is a newly emerging and potent form of cancer immunotherapy and has clinically relevant mechanisms of action with great potential for the systemic treatment of cancers. However, clinical trials have demonstrated relatively poor therapeutic efficacy. The efficacy of DC-vaccines is strongly influenced by various techniques for the priming antigen loading onto DCs and their ability to migrate to the draining lymph nodes (LNs)...
2017: American Journal of Cancer Research
https://www.readbyqxmd.com/read/29118918/image-guided-dendritic-cell-based-vaccine-immunotherapy-in-murine-carcinoma-models
#11
REVIEW
Bin Wang, Chong Sun, Sijia Wang, Na Shang, Matteo Figini, Quanhong Ma, Shanzhi Gu, Daniele Procissi, Vahid Yaghmai, Guoxin Li, Andrew Larson, Zhuoli Zhang
In recent decades, immunotherapy has undergone extensive developments for oncologic therapy applications. Dendritic cells (DCs) plays a fundamental role in cell-based vaccination immunotherapy against various types of cancer. It involves stimulating innate and adaptive immunity, in particular cytotoxic T-cell mediated antitumor effects, against targeted tumors and has been studied in both preclinical and clinical settings. Nevertheless, clinical outcomes have been unsatisfying. The antitumor response requires sufficient migration of viable DCs from primary administration site to targeted tumors through related lymphatics...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/29114544/dendritic-cell-therapy-in-melanoma
#12
REVIEW
Carmen Alvarez-Dominguez, Ricardo Calderón-Gonzalez, Hector Terán-Navarro, David Salcines-Cuevas, Almudena Garcia-Castaño, Javier Freire, Javier Gomez-Roman, Fernando Rivera
Dendritic cell (DC) vaccines are cancer vaccines used currently as melanoma therapies. They act as adjuvants initiating the immune responses, but not only as they can also have effector activities redirecting cytotoxic CD8(+) T cells against melanoma. Ex vivo preparation of monocyte derived DCs has been implemented to produce large numbers of DCs for clinical therapy, highlighting the necessity of activate DC s to produce Th1 cytokines, especially TNF-a and IL-12 with potent anti-tumour actions. Several clinical trials both in the European Union and USA are open currently using DC vaccines, alone or in combination with other immunotherapies...
October 2017: Annals of Translational Medicine
https://www.readbyqxmd.com/read/29112931/comparison-of-fusion-protein-and-dc-vaccine-in-inhibition-of-mouse-b16f10-melanoma-tumor
#13
Yan Zhang, Xiaoxin Liu, Rui Wang, Shujun Liu, Yiqin Wang, Liangliang Jing, Meko'o Didier Jean Louis, Rongyue Cao
Dendritic cell (DC) vaccine and fusion protein vaccine have been put into clinical use in cancer immunotherapy. This study compared DC vaccine and fusion protein vaccine directly in their capability of inducing specific immune response. We used mouse Granulocyte Macrophage-Colony Stimulating Factor (mGM-CSF) fused with gastrin-releasing peptide (GRP) and Gonadotrophin Releasing Hormone (GnRH) respectively to obtain mGM-CSF/GRP6 (mG6) and mGM-CSF/mGGn (mGGn) fusion proteins. We prepared fusion protein vaccine and DC vaccine including mG6 protein vaccine (6P), mGGn protein vaccine (nP), mG6 DC vaccine (6D) and mGGn DC vaccine (nD), then the two proteins were mixed to prepare combination proteins vaccine (6nP) and DC vaccine (6nD)...
November 4, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29109732/ccl3-enhances-antitumor-immune-priming-in-the-lymph-node-via-ifn%C3%AE-with-dependency-on-natural-killer-cells
#14
Frederick Allen, Peter Rauhe, David Askew, Alexander A Tong, Joseph Nthale, Saada Eid, Jay T Myers, Caryn Tong, Alex Y Huang
Lymph node (LN) plays a critical role in tumor cell survival outside of the primary tumor sites and dictates overall clinical response in many tumor types (1, 2). Previously, we and others have demonstrated that CCL3 plays an essential role in orchestrating T cell-antigen-presenting cell (APC) encounters in the draining LN following vaccination, and such interactions enhance the magnitude of the memory T cell pool (3-5). In the current study, we investigate the cellular responses in the tumor-draining lymph nodes (TDLNs) of a CCL3-secreting CT26 colon tumor (L3TU) as compared to wild-type tumor (WTTU) during the priming phase of an antitumor response (≤10 days)...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29104773/antitumor-vaccines-based-on-dendritic-cells-from-experiments-using-animal-tumor-models-to-clinical-trials
#15
O V Markov, N L Mironova, V V Vlassov, M A Zenkova
The routine methods used to treat oncological diseases have a number of drawbacks, including non-specific action and severe side effects for patients. Furthermore, tumor diseases are associated with a suppression of the immune system that often leads to the inefficiency of standard treatment methods. The development of novel immunotherapeutic approaches having specific antitumor action and that activate the immune system is of crucial importance. Vaccines based on dendritic cells (DCs) loaded with tumor antigens ex vivo that can activate antitumor cytotoxic T-cell responses stand out among different antitumor immunotherapeutic approaches...
July 2017: Acta Naturae
https://www.readbyqxmd.com/read/29103998/tlr8-combined-withtlr3-or-tlr4-agonists-enhances-dc-nk-driven-effector-tc1-cells
#16
Mahyar Nouri-Shirazi, Saba Tamjidi, Erika Nourishirazi, Elisabeth Guinet
BACKGROUND: Most current prophylactic vaccines confer protection primarily through humoral immunity. Indeed, aluminum salts which have been widely used as adjuvants in vaccines primarily enhance Th2-driven antibody responses. Therefore, new vaccines formulation is moving toward a careful selection of adjuvants that also elicit significant Th1 or Tc1 responses. Several TLR agonists have been tested as potential new adjuvants in clinical and preclinical studies with some efficacy. These studies suggest that combining more than one of TLR ligands enhances the magnitude of immune responses to cancer and infectious disease...
November 2, 2017: Immunology Letters
https://www.readbyqxmd.com/read/29094184/braf-peptide-vaccine-facilitates-therapy-of-murine-braf-mutant-melanoma
#17
Qi Liu, Hongda Zhu, Yun Liu, Sara Musetti, Leaf Huang
Approximately, 50% of human melanomas are driven by BRAF mutations, which produce tumors that are highly immunosuppressive and often resistant to vaccine therapy. We introduced lipid-coated calcium phosphate nanoparticles (LCP NPs) as a carrier to efficiently deliver a tumor-specific antigen, the BRAF(V600E) peptide, to drive dendritic cell (DC) maturation and antigen presentation in C57BL6 mice. The BRAF peptide vaccine elicited a robust, antigen-specific cytotoxic T cell response and potent tumor growth inhibition in a murine BRAF-mutant melanoma model...
November 1, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/29093005/dendritic-cells-enhance-polyfunctionality-of-adoptively-transferred-t-cells-which-target-cytomegalovirus-in-glioblastoma
#18
Elizabeth Reap, Carter M Suryadevara, Kristen A Batich, Luis Sanchez-Perez, Gary E Archer, Robert J Schmittling, Pamela K Norberg, James E Herndon, Patrick Healy, Kendra L Congdon, Patrick C Gedeon, Olivia C Campbell, Adam M Swartz, Katherine A Riccione, John S Yi, Mohammed K Hossain-Ibrahim, Anirudh Saraswathula, Smita K Nair, Anastasie M Dunn-Pirio, Taylor M Broome, Kent J Weinhold, Annick Desjardins, Gordana Vlahovic, Roger Mclendon, Allan H Friedman, Henry S Friedman, Darell D Bigner, Peter E Fecci, Duane A Mitchell, John H Sampson
Median survival for glioblastoma (GBM) remains <15 months. Human Cytomegalovirus (CMV) antigens have been identified in GBM but not normal brain, providing an unparalleled opportunity to subvert CMV antigens as tumor-specific immunotherapy targets. A recent trial in recurrent GBM patients demonstrated the potential clinical benefit of adoptive T cell therapy (ATCT) of CMV phosphoprotein 65 (pp65)-specific T cells. However, ex vivo analyses from this study found no change in the capacity of CMV pp65-specific T cells to gain multiple effector functions or polyfunctionality, which has been associated with superior antitumor efficacy...
November 1, 2017: Cancer Research
https://www.readbyqxmd.com/read/29079801/development-of-a-curative-therapeutic-vaccine-theravac-for-the-treatment-of-large-established-tumors
#19
Yingjie Nie, De Yang, Anna Trivett, Zhen Han, Haiyun Xin, Xin Chen, Joost J Oppenheim
Harnessing immune system to treat cancer requires simultaneous generation of tumor-specific CTLs and curtailment of tumor immunosuppressive environment. Here, we developed an immunotherapeutic regimen capable of eliminating large established mouse tumors using HMGN1, a DC-activating TLR4 agonist capable of inducing anti-tumor immunity. Intratumoral delivery of HMGN1 with low dose of Cytoxan cured mice bearing small (∅ ≈ 0.5 cm), but not large (∅ ≈ 1.0 cm) CT26 tumors. Screening for activators capable of synergizing with HMGN1 in activating DC identified R848...
October 27, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29079105/immunization-against-full-length-protein-and-peptides-from-the-lutzomyia-longipalpis-sand-fly-salivary-component-maxadilan-protects-against-leishmania-major-infection-in-a-murine-model
#20
William H Wheat, Erik N Arthun, John S Spencer, Daniel P Regan, Richard G Titus, Steven W Dow
Leishmaniasis is an arthropod vectored disease causing considerable human morbidity and mortality. Vaccination remains the most realistic and practical means to interrupt the growing number and diversity of sand fly vectors and reservoirs of Leishmania. Since transmission of Leishmania is achieved exclusively by sand fly vectors via immune-modulating salivary substances, conventional vaccination requiring an unmodified host immune response for success are potentially destined to fail unless immunomodulatory factors are somehow neutralized...
October 24, 2017: Vaccine
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