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https://www.readbyqxmd.com/read/28819024/trastuzumab-increases-her2-uptake-and-cross-presentation-by-dendritic-cells
#1
Victor A Gall, Anne V Philips, Na Qiao, Karen Clise-Dwyer, Alexander A Perakis, Mao Zhang, Guy Travis Clifton, Pariya Sukhumalchandra, Qing Ma, Sangeetha M Reddy, Dihua Yu, Jeffrey J Molldrem, George E Peoples, Gheath Alatrash, Elizabeth A Mittendorf
Early phase clinical trials evaluating CD8+ T cell-eliciting, HER2-derived peptide vaccines administered to HER2-positive breast cancer patients in the adjuvant setting suggest synergy between the vaccines and trastuzumab, the monoclonal antibody targeting the HER2 protein. Among 60 patients enrolled on clinical trials evaluating the E75+GM-CSF and GP2+GM-CSF vaccines, there have been no recurrences in patients vaccinated after receiving trastuzumab as part of standard therapy in the per treatment analyses conducted after a median follow-up of greater than 34 months...
August 17, 2017: Cancer Research
https://www.readbyqxmd.com/read/28811970/trial-watch-dendritic-cell-based-anticancer-immunotherapy
#2
REVIEW
Abhishek D Garg, Monica Vara Perez, Marco Schaaf, Patrizia Agostinis, Laurence Zitvogel, Guido Kroemer, Lorenzo Galluzzi
Dendritic cell (DC)-based vaccines against cancer have been extensively developed over the past two decades. Typically DC-based cancer immunotherapy entails loading patient-derived DCs with an appropriate source of tumor-associated antigens (TAAs) and efficient DC stimulation through a so-called "maturation cocktail" (typically a combination of pro-inflammatory cytokines and Toll-like receptor agonists), followed by DC reintroduction into patients. DC vaccines have been documented to (re)activate tumor-specific T cells in both preclinical and clinical settings...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28811965/adjuvant-immunotherapy-with-autologous-dendritic-cells-for-hepatocellular-carcinoma-randomized-phase-ii-study
#3
Jeong-Hoon Lee, Won Young Tak, Yoon Lee, Min-Kyu Heo, Jae-Sung Song, Hak-Yeop Kim, Soo Young Park, Si Hyun Bae, Joon Hyeok Lee, Jeong Heo, Ki-Hwan Kim, Yong-Soo Bae, Yoon Jun Kim
Our previous phase I/IIA study showed that autologous dendritic cells (DCs) pulsed with tumor-associated antigens are well tolerated in patients with hepatocellular carcinoma (HCC). In this randomized, multicenter, open-label, phase II trial, we investigated the efficacy and safety of this DC-based adjuvant immunotherapy with 156 patients, who treated for HCC with no evidence of residual tumor after standard treatment modalities. Patients were randomly assigned to immunotherapy (n = 77; injection of 3 × 10(7) DC cells, six times over 14 weeks) or control (n = 79; no treatment)...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28807659/expanding-state-laws-and-a-growing-role-for-pharmacists-in-vaccination-services
#4
Cason D Schmit, Matthew S Penn
OBJECTIVES: Gaps in vaccination coverage leave populations vulnerable to illnesses. Since the 1990s, there has been a growing movement to improve vaccination access by giving pharmacists the authority to administer vaccines according to state laws. Understanding the variation of pharmacist vaccination laws over time is critical to understanding the effect of improving access to vaccination services. METHODS: We identified relevant statutes and regulations with the use of Westlaw legal databases...
August 11, 2017: Journal of the American Pharmacists Association: JAPhA
https://www.readbyqxmd.com/read/28802641/enhanced-effects-of-dna-vaccine-against-botulinum-neurotoxin-serotype-a-by-targeting-antigen-to-dendritic-cells
#5
Bo-Yang Chen, Guo Zhou, Qing-Li Li, Jian-Sheng Lu, Dan-Yang Shi, Xiao-Bin Pang, Xiao-Wei Zhou, Yun-Zhou Yu, Pei-Tang Huang
As dendritic cells (DCs) play a critical role in priming antigen-specific immune responses, the efficacy of DNA vaccines may be enhanced by targeting the encoded antigen proteins to DCs. In this study, we constructed a DC-targeted DNA vaccine encoding the Hc domain of botulinum neurotoxin serotype A (AHc) fused with scDEC, a single-chain Fv antibody (scFv) specific for the DC-restricted antigen-uptake receptor DEC205. Intramuscular injections of mice with the DC-targeted DNA vaccine (pVAX1-scDEC-AHc) stimulated more DCs to mature than the non-targeted DNA vaccine (pVAX1-SAHc) in the splenocytes...
August 9, 2017: Immunology Letters
https://www.readbyqxmd.com/read/28792466/distinctive-responses-in-an-in-vitro-human-dendritic-cell-based-system-upon-stimulation-with-different-influenza-vaccine-formulations
#6
Gabriela Tapia-Calle, Maaike Stoel, Jacqueline de Vries-Idema, Anke Huckriede
Vaccine development relies on testing vaccine candidates in animal models. However, results from animals cannot always be translated to humans. Alternative ways to screen vaccine candidates before clinical trials are therefore desirable. Dendritic cells (DCs) are the main orchestrators of the immune system and the link between innate and adaptive responses. Their activation by vaccines is an essential step in vaccine-induced immune responses. We have systematically evaluated the suitability of two different human DC-based systems, namely the DC-cell line MUTZ-3 and primary monocyte-derived DCs (Mo-DCs) to screen immunopotentiating properties of vaccine candidates...
August 9, 2017: Vaccines
https://www.readbyqxmd.com/read/28789525/direct-loading-of-itep-delivered-ctl-epitopes-onto-mhc-class-i-complexes-on-the-dendritic-cell-surface
#7
Shuyun Dong, Peng Wang, Peng Zhao, Mingnan Chen
Cytotoxic T lymphocyte (CTL)-mediated immune responses are the primary defense mechanism against cancer and infection. CTL epitope peptides have been used as vaccines to boost CTL responses; however, the efficacy of these peptides is suboptimal. Under current vaccine formulation and delivery strategies, these vaccines are delivered into and processed inside antigen presenting cells such as dendritic cells (DCs). However, the intracellular process is not efficient, which at least partially contributes to the suboptimal efficacy of the vaccines...
August 8, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28763347/ex-vivo-induction-of-multiple-myeloma-specific-immune-responses-by-monocyte-derived-dendritic-cells-following-stimulation-by-whole-tumor-antigen-of-autologous-myeloma-cells
#8
Spyridoula Vasileiou, Ioannis Baltadakis, Sosanna Delimpasi, Maria-Helena Karatza, Konstantinos Liapis, Maria Garofalaki, Eirini Tziotziou, Zoe Poulopoulou, Dimitri Karakasis, Nicholas Harhalakis
The introduction of novel agents has significantly expanded treatment options for multiple myeloma (MM), albeit long-term disease control cannot be achieved in the majority of patients. Vaccination with MM antigen-loaded dendritic cells (DCs) represents an alternative strategy that is currently being explored. The aim of this study was to assess the immunogenic potential of ex vivo-generated monocyte-derived DCs (moDCs), following stimulation with the whole-antigen array of autologous myeloma cells (AMC). MoDCs were loaded with antigens of myeloma cells by 2 different methods: phagocytosis of apoptotic bodies from γ-irradiated AMC, or transfection with AMC total RNA by square-wave electroporation...
July 31, 2017: Journal of Immunotherapy
https://www.readbyqxmd.com/read/28759159/peptosomes-for-vaccination-combining-antigen-and-adjuvant-in-polypept-o-ide-based-polymersomes
#9
Benjamin Weber, Cinja Kappel, Martin Scherer, Mark Helm, Matthias Bros, Stephan Grabbe, Matthias Barz
In this work, the first vaccine is reported based on a PeptoSome, which contains a model antigen (SIINFEKL) and adjuvant (CpG). PeptoSomes are polypept(o)ide-based polymersomes built of a block-copolymer with polysarcosine (PSar) as the hydrophilic block (X n = 111) and poly(benzyl-glutamic acid) (PGlu(OBn)) as the hydrophobic one (X n = 46). The polypept(o)ide is obtained with low dispersity index of 1.32 by controlled ring-opening polymerization. Vesicle formation by dual centrifugation technique allows for loading of vesicles up to 40 mol%...
July 31, 2017: Macromolecular Bioscience
https://www.readbyqxmd.com/read/28756536/therapeutic-blockade-of-foxp3-in-experimental-breast-cancer-models
#10
Mariela A Moreno Ayala, María Florencia Gottardo, Mercedes Imsen, Antonela S Asad, Elisa Bal de Kier Joffé, Noelia Casares, Juan José Lasarte, Adriana Seilicovich, Marianela Candolfi
PURPOSE: Regulatory T cells (Tregs) impair the clinical benefit of cancer immunotherapy. To optimize the antitumor efficacy of therapeutic dendritic cell (DC) vaccines, we aimed to inhibit Foxp3, a transcription factor required for Treg function. METHODS: Mice bearing established syngeneic LM3 and 4T1 breast tumors were treated with antitumor DC vaccines and a synthetic peptide (P60) that has been shown to inhibit Foxp3. RESULTS: Treatment with P60 improved the therapeutic efficacy of DC vaccines in these experimental models...
July 29, 2017: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/28743486/targeting-interferon-alpha-to-dendritic-cells-enhances-a-cd8-t-cell-response-to-a-human-cd40-targeted-cancer-vaccine
#11
John P Graham, Pierre Authie, A Karolina Palucka, Gerard Zurawski
Targeting antigens to antigen presenting cells (APC) enhances the potency of recombinant protein CD8(+) T cell vaccines. Recent comparisons of recombinant protein-based dendritic cell (DC) targeting vaccines revealed differences in cross-presentation and identified CD40 as a potent human DC receptor target for antigen cross-presentation. Contrary to in vitro-derived monocyte (mo)DC, we found that interferon-alpha (IFNα) stimulation of human blood-derived DC was necessary for an antigen-specific IFNγ CD8(+) T cell response to a CD40 targeted cancer vaccine...
July 22, 2017: Vaccine
https://www.readbyqxmd.com/read/28740382/dual-linker-gold-nanoparticles-as-adjuvanting-carriers-for-multivalent-display-of-recombinant-influenza-hemagglutinin-trimers-and-flagellin-improve-the-immunological-responses-in-vivo-and-in-vitro
#12
Chao Wang, Wandi Zhu, Bao-Zhong Wang
Vaccination is the most cost-effective means of infectious disease control. Although current influenza vaccines are effective in battling closely matched strains, such vaccines have major limitations such as the requirement to produce new vaccines every season, an egg-dependent production system, long production periods, uncertainty in matching the vaccine to circulating strains, and the inability to react to new influenza pandemics resulting from genetic drift or shift. To overcome the intrinsic limitations of the conventional influenza vaccine, we have designed dual-linker gold nanoparticles (AuNPs) conjugated with both recombinant trimetric A/Aichi/2/68 (H3N2), hemagglutinin (HA) and TLR5 agonist flagellin (FliC) as a novel vaccine approach...
2017: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/28740080/a-new-marine-derived-sulfoglycolipid-triggers-dendritic-cell-activation-and-immune-adjuvant-response
#13
Emiliano Manzo, Adele Cutignano, Dario Pagano, Carmela Gallo, Giusi Barra, Genoveffa Nuzzo, Clementina Sansone, Adrianna Ianora, Konrad Urbanek, Daniela Fenoglio, Francesca Ferrera, Cinzia Bernardi, Alessia Parodi, Giuseppe Pasquale, Antonio Leonardi, Gilberto Filaci, Raffaele De Palma, Angelo Fontana
Dendritic Cells (DCs) recognize infectious non-self molecules and engage the adaptive immune system thereby initiating long lasting, antigen-specific responses. As such, the ability to activate DCs is considered a key tool to enhance the efficacy and quality of vaccination. Here we report a novel immunomodulatory sulfolipid named β-SQDG18 that prototypes a class of natural-derived glycolipids able to prime human DCs by a TLR2/TLR4-independent mechanism and trigger an efficient immune response in vivo. β-SQDG18 induces maturation of DC with the upregulation of MHC II molecules and co-stimulatory proteins (CD83, CD86), as well as pro-inflammatory cytokines (IL-12 and INF-γ)...
July 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28734965/enhanced-immunostimulatory-activity-of-in-silico-discovered-agonists-of-toll-like-receptor-2-tlr2
#14
M S Murgueitio, S Ebner, P Hörtnagl, C Rakers, R Bruckner, P Henneke, G Wolber, S Santos-Sierra
BACKGROUND: Emergent therapies in anticancer vaccination use Toll-like receptors (TLRs) agonists as dendritic cell (DC) vaccine adjuvants. DCs from the patient are isolated, stimulated with TLR agonists and tumor antigens ex vivo and then infused back into the patient. Although some TLR ligands have been tested in clinical trials, novel TLR agonists with improved immunomodulatory properties are essential to optimize treatment success. We report on the discovery of small-molecule TLR2 agonists, with favorable properties as synthetic adjuvants...
July 19, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28732279/turbocharging-vaccines-emerging-adjuvants-for-dendritic-cell-based-therapeutic-cancer-vaccines
#15
REVIEW
Mansi Saxena, Nina Bhardwaj
Development of therapeutic cancer vaccines has been hindered by the many pro-tumorigenic mechanisms at play in cancer patients that serve to suppress both antigen presenting cells and T cells. In face of these obstacles, cancer vaccines are most likely to promote anti-tumorigenic immune responses only when formulated with strong adjuvants, and in combination with new immune interventions designed to reverse immune suppression and exhaustion of T cells in the tumor microenvironment. Dendritic cells (DCs) are often termed 'nature's adjuvant' due to their exceptional capacity for initiating both innate and adaptive immune responses...
July 18, 2017: Current Opinion in Immunology
https://www.readbyqxmd.com/read/28722020/a-critical-role-of-gas6-axl-signal-in-allergic-airway-responses-during-rsv-vaccine-enhanced-disease
#16
Takehiko Shibata, Manabu Ato
Respiratory syncytial virus (RSV) is a common virus that causes lower respiratory infections across a wide range of ages. A licensed RSV vaccine is not available because vaccination with formalin-inactivated RSV (FI-RSV) and the subsequent RSV infection cause not only insufficient induction of neutralizing antibodies but also severe allergic airway responses, termed FI-RSV vaccine enhanced disease (FI-RSV VED). However, the underlying mechanism has not been identified, although a Th2-biased immune response is known to be a hallmark of this disease...
July 19, 2017: Immunology and Cell Biology
https://www.readbyqxmd.com/read/28720467/intradermal-immunization-with-raav1-vector-induces-robust-memory-cd8-t-cell-responses-independently-of-transgene-expression-in-dcs
#17
Alexandre Ghenassia, David-Alexandre Gross, Stéphanie Lorain, Fabiola Tros, Dominique Urbain, Sofia Benkhelifa-Ziyyat, Alain Charbit, Jean Davoust, Pascal Chappert
Recombinant adeno-associated viral (rAAV) vectors exhibit interesting properties as vaccine carriers for their ability to induce long-lasting antibody responses. However, rAAV-based vaccines have been suggested to trigger functionally impaired long-term memory CD8(+) T cell responses, in part due to poor dendritic cell (DC) transduction. Such results, albeit limited to intramuscular immunization, undermined the use of rAAV as vaccine vehicles against intracellular pathogens. We report here that intradermal immunization with a model rAAV2/1-based vaccine drives the development of bona fide long-term memory CD8(+) T cell responses...
July 15, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28714508/gold-glyconanoparticles-coupled-to-listeriolysin-o-91-99-peptide-serve-as-adjuvant-therapy-against-melanoma
#18
R Calderon-Gonzalez, H Terán-Navarro, I García, M Marradi, D Salcines-Cuevas, S Yañez-Diaz, A Solis-Angulo, E Frande-Cabanes, M C Fariñas, A Garcia-Castaño, J Gomez-Roman, S Penades, F Rivera, J Freire, C Álvarez-Domínguez
Dendritic cell-based (DC-based) vaccines are promising immunotherapies for cancer. However, several factors, such as the lack of efficient targeted delivery and the sources and types of DCs, have limited the efficacy of DCs and their clinical potential. We propose an alternative nanotechnology-based vaccine platform with antibacterial prophylactic abilities that uses gold glyconanoparticles coupled to listeriolysin O 91-99 peptide (GNP-LLO91-99), which acts as a novel adjuvant for cancer therapy. GNP-LLO91-99, when used to vaccinate mice, exhibited dual antitumour activities, namely, the inhibition of tumour migration and growth and adjuvant activity for recruiting and activating DCs, including those from melanoma patients...
August 3, 2017: Nanoscale
https://www.readbyqxmd.com/read/28713366/intratumoral-lentivector-mediated-tgf-%C3%AE-1-gene-downregulation-as-a-potent-strategy-for-enhancing-the-antitumor-effect-of-therapy-composed-of-cyclophosphamide-and-dendritic-cells
#19
Joanna Rossowska, Natalia Anger, Agnieszka Szczygieł, Jagoda Mierzejewska, Elżbieta Pajtasz-Piasecka
Vaccination with dendritic cells (DCs) stimulated with tumor antigens can induce specific cellular immune response that recognizes a high spectrum of tumor antigens. However, the ability of cancer cells to produce immunosuppressive factors drastically decreases the antitumor activity of DCs. The main purpose of the study was to improve the effectiveness of DC-based immunotherapy or chemoimmunotherapy composed of cyclophosphamide (CY) and DCs by application of lentivectors (LVs)-encoding short hairpin RNA specific for TGF-β1 (shTGFβ1 LVs)...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28713023/an-extended-mathematical-model-of-tumor-growth-and-its-interaction-with-the-immune-system-to-be-used-for-developing-an-optimized-immunotherapy-treatment-protocol
#20
Milad Qomlaqi, Fariba Bahrami, Maryam Ajami, Jamshid Hajati
BACKGROUND: Chemotherapy is usually known as the main modality for cancer treatment. Nevertheless, most of chronic cancers could not be treated with chemotherapy alone. Immunotherapy is a new modality for cancer treatment that is effective for early stages of cancer and it has fewer side effects compared to chemotherapy, specifically for those types of cancer that are resistant to it. METHOD: This work presents an extended mathematical model to depict interactions between cancerous and adaptive immune system in mouse...
July 14, 2017: Mathematical Biosciences
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