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Dendritic cell vaccine

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https://www.readbyqxmd.com/read/28223987/dendritic-cell-targeting-effectively-boosts-t-cell-responses-elicited-by-an-hiv-multiepitope-dna-vaccine
#1
Juliana de Souza Apostólico, Victória Alves Santos Lunardelli, Marcio Massao Yamamoto, Higo Fernando Santos Souza, Edecio Cunha-Neto, Silvia Beatriz Boscardin, Daniela Santoro Rosa
Despite several efforts in the last decades, an efficacious HIV-1 vaccine is still not available. Different approaches have been evaluated, such as recombinant proteins, viral vectors, DNA vaccines, and, most recently, dendritic cell (DC) targeting. This strategy is based on DC features that place them as central for induction of immunity. Targeting is accomplished by the use of chimeric monoclonal antibodies directed to DC surface receptors fused to the antigen of interest. In this work, we targeted eight promiscuous HIV-derived CD4(+) T cell epitopes (HIVBr8) to the DEC205(+) DCs by fusing the multiepitope immunogen to the heavy chain of αDEC205 (αDECHIVBr8), in the presence of the TLR3 agonist poly (I:C)...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28222998/dynamics-of-apc-recruitment-at-the-site-of-injection-following-injection-of-vaccine-adjuvants
#2
Susan van Aalst, Irene Stephanie Ludwig, Peter Johannes Sylvester van Kooten, Ruurd van der Zee, Willem van Eden, Femke Broere
Vaccines often contain adjuvants to strengthen the response to the vaccine antigen. However, their modes of action at the site of injection (SOI) are poorly understood. Therefore, we assessed the local effects of adjuvant on the innate immune system in mice. We investigated the safe, widely used adjuvants MF59 and aluminum hydroxide (alum), as well as trehalose-6,6'-dibehenate (TDB), Complete Freund's Adjuvant (CFA) and the Toll-Like-Receptor-ligands lipopolysaccharide (LPS) and Pam3CysSerLys4 (Pam3CSK4). We assessed muscle immune cell infiltration after adjuvant injection and observed 16h post immunization (hpi) an increased influx with CFA, MF59 and TDB, but not with alum, LPS or Pam3CSK4...
February 17, 2017: Vaccine
https://www.readbyqxmd.com/read/28219022/rationale-for-stimulator-of-interferon-genes-targeted-cancer-immunotherapy
#3
REVIEW
Thaiz Rivera Vargas, Isis Benoit-Lizon, Lionel Apetoh
The efficacy of checkpoint inhibitor therapy illustrates that cancer immunotherapy, which aims to foster the host immune response against cancer to achieve durable anticancer responses, can be successfully implemented in a routine clinical practice. However, a substantial proportion of patients does not benefit from this treatment, underscoring the need to identify alternative strategies to defeat cancer. Despite the demonstration in the 1990's that the detection of danger signals, including the nucleic acids DNA and RNA, by dendritic cells (DCs) in a cancer setting is essential for eliciting host defence, the molecular sensors responsible for recognising these danger signals and eliciting anticancer immune responses remain incompletely characterised, possibly explaining the disappointing results obtained so far upon the clinical implementation of DC-based cancer vaccines...
February 17, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28215994/safe-recombinant-outer-membrane-vesicles-that-display-m2e-elicit-heterologous-influenza-protection
#4
Hannah C Watkins, C Garrett Rappazzo, Jaclyn S Higgins, Xiangjie Sun, Nicole Brock, Annie Chau, Aditya Misra, Joseph P B Cannizzo, Michael R King, Taronna R Maines, Cynthia A Leifer, Gary R Whittaker, Matthew P DeLisa, David Putnam
Recombinant, Escherichia coli-derived outer membrane vesicles (rOMVs), which display heterologous protein subunits, have potential as a vaccine adjuvant platform. One drawback to rOMVs is their lipopolysaccharide (LPS) content, limiting their translatability to the clinic due to potential adverse effects. Here, we explore a unique rOMV construct with structurally remodeled lipids containing only the lipid IVa portion of LPS, which does not stimulate human TLR4. The rOMVs are derived from a genetically engineered B strain of E...
February 16, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28215654/dendritic-cell-vaccination-in-combination-with-docetaxel-for-patients-with-metastatic-castration-resistant-prostate-cancer-a-randomized-phase-ii-study
#5
Per Kongsted, Troels Holz Borch, Eva Ellebaek, Trine Zeeberg Iversen, Rikke Andersen, Özcan Met, Morten Hansen, Henriette Lindberg, Lisa Sengeløv, Inge Marie Svane
BACKGROUND AIMS: We investigated whether the addition of an autologous dendritic cell-based cancer vaccine (DCvac) induces an immune response in patients with metastatic castration-resistant prostate cancer treated with docetaxel. METHODS: Forty-three patients were randomized 1:1 to receive up to 10 cycles of docetaxel alone, 75 mg/m(2) every 3 weeks or in combination with DCvac. Monocytes were harvested following a leukapheresis procedure, matured ex vivo and subsequently transfected with messenger RNA encoding multiple tumor-associated antigens (TAAs)...
February 15, 2017: Cytotherapy
https://www.readbyqxmd.com/read/28215530/rationale-for-the-combination-of-dendritic-cell-based-vaccination-approaches-with-chemotherapy-agents
#6
I Truxova, M Hensler, P Skapa, M J Halaska, J Laco, A Ryska, R Spisek, J Fucikova
Owing to their central role in the initiation and regulation of antitumor immunity, dendritic cells (DCs) have been widely tested for use in cancer immunotherapy. Despite several encouraging clinical applications, existing DC-based immunotherapy efforts have yielded inconsistent results. Recent work has identified strategies that may allow for more potent DC-based vaccines, such as the combination with antitumor agents that have the potential to synergistically enhance DC functions. Selected cytotoxic agents may stimulate DCs either by directly promoting their maturation or through the induction of immunogenic tumor cell death...
2017: International Review of Cell and Molecular Biology
https://www.readbyqxmd.com/read/28212670/characterization-of-schistosoma-japonicum-cp1412-protein-as-a-novel-member-of-the-ribonuclease-t2-molecule-family-with-immune-regulatory-function
#7
Xue-Dan Ke, Shuang Shen, Li-Jun Song, Chuan-Xin Yu, Mihoko Kikuchi, Kenji Hirayama, Hong Gao, Jie Wang, Xuren Yin, Yuan Yao, Qian Liu, Wei Zhou
BACKGROUND: Schistosome infection typically induces a polarized Th2 type host immune response. As egg antigen molecules play key roles in this immunoregulatory process, clarifying their functions in schistosomiasis would facilitate the development of vaccine and immunotherapeutic methods. Schistosoma japonicum (Sj) CP1412 (GenBank: AY57074.1) has been identified as a new member of the RNase T2 family with immune regulatory functions. METHODS: The expression plasmid Sj CP1412-pET28a was constructed and transformed into bacteria for production of recombinant Sj CP1412 protein (rSj CP1412) via IPTG induction...
February 17, 2017: Parasites & Vectors
https://www.readbyqxmd.com/read/28209996/transient-cannabinoid-receptor-2-blockade-during-immunization-heightens-intensity-and-breadth-of-antigen-specific-antibody-responses-in-young-and-aged-mice
#8
Emmanuel Dotsey, Irina Ushach, Egest Pone, Rie Nakajima, Algis Jasinskas, Donovan A Argueta, Andrea Dillon, Nicholas DiPatrizio, Huw Davies, Albert Zlotnik, Peter D Crompton, Philip L Felgner
The hallmark of vaccines is their ability to prevent the spread of infectious pathogens and thereby serve as invaluable public health tool. Despite their medical relevance, there is a gap in our understanding of the physiological factors that mediate innate and adaptive immune response to vaccines. The endocannabinoid (eCB) system is a critical modulator of homeostasis in vertebrates. Our results indicate that macrophages and dendritic cells produce the endocannabinoid, 2-arachidonoyl-sn-glycerol (2-AG) upon antigen activation...
February 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28205361/immunotherapy-against-metastatic-bladder-cancer-by-combined-administration-of-granulocyte-macrophage-colony-stimulating-factor-and-interleukin-2-surface-modified-mb49-bladder-cancer-stem-cells-vaccine
#9
Chun-Yan Wang, Rui Hua, Li Liu, Xiaomin Zhan, Simei Chen, Song Quan, Qing-Jun Chu, Yong-Tong Zhu
In previous studies, it has been shown that the granulocyte macrophage-colony stimulating factor (GM-CSF) or interleukin-2 (IL-2) surface modified MB49 bladder cancer stem cells (MCSCs) vaccine could induce a specific antitumor immunity and against bladder cancer in mice model respectively. However, whether combined administration of GM-CSF and IL-2 could produce specific immune responses to cancer stem cells (CSCs) was uncertain. MCSCs were established and characterized. GM-CSF and IL-2 MCSCs vaccines were prepared and bioactivity was evaluated...
February 16, 2017: Cancer Medicine
https://www.readbyqxmd.com/read/28203287/specific-immunotherapy-in-renal-cancer-a-systematic-review
#10
REVIEW
Armin Hirbod-Mobarakeh, Hesam Addin Gordan, Zahra Zahiri, Mohammad Mirshahvalad, Sima Hosseinverdi, Brian I Rini, Nima Rezaei
BACKGROUND: Renal cell cancer (RCC) is the tenth most common malignancy in adults. In recent years, several approaches of active and passive immunotherapy have been studied extensively in clinical trials of patients with RCC. The aim of this systematic review was to assess the clinical efficacy of various approaches of specific immunotherapy in patients with RCC. METHODS: We searched Medline, Scopus, CENTRAL, TRIP, DART, OpenGrey and ProQuest without any language filter through to 9 October 2015...
February 2017: Therapeutic Advances in Urology
https://www.readbyqxmd.com/read/28202751/superiority-in-rhesus-macaques-of-targeting-hiv-1-env-gp140-to-cd40-versus-lox-1-in-combination-with-replication-competent-nyvac-kc-for-induction-of-env-specific-antibody-and-t-cell-responses
#11
Gerard Zurawski, Xiaoying Shen, Sandra Zurawski, Georgia D Tomaras, David C Montefiori, Mario Roederer, Guido Ferrari, Christine Lacabaratz, Peter Klucar, Zhiqing Wang, Kathryn E Foulds, Shing-Fen Kao, Xuesong Yu, Alicia Sato, Nicole L Yates, Celia LaBranche, Sherry Stanfield-Oakley, Karen Kibler, Bertram Jacobs, Andres Salazar, Steve Self, Jimmy Fulp, Raphael Gottardo, Lindsey Galmin, Deborah Weiss, Anthony Cristillo, Giuseppe Pantaleo, Yves Levy
We compared the HIV-1-specific immune responses generated by targeting HIV-1 envelope protein (Env gp140) to either CD40 or LOX-1, two endocytic receptors on dendritic cells (DCs), in Rhesus macaques primed with a poxvirus vector (NYVAC-KC) expressing Env gp140. The DC-targeting vaccines, humanized recombinant monoclonal antibodies fused to Env gp140, were administered as a boost with poly ICLC adjuvant either alone or co-administered with the NYVAC-KC vector. All the DC-targeting vaccine administrations with poly ICLC increased the low-level serum anti-Env IgG responses elicited by NYVAC-KC priming significantly more (up to P =0...
February 15, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28202532/cd40-signaling-drives-potent-cellular-immune-responses-in-heterologous-cancer-vaccinations
#12
Supot Nimanong, Dmitrij Ostroumov, Jessica Wingerath, Sarah Knocke, Norman Woller, Engin Guerlevik, Christine Falk, Michael P Manns, Florian Kuehnel, Thomas C Wirth
Antagonistic antibodies targeting co-inhibitory receptors have revolutionized the treatment of cancer by inducing durable immune responses and clinical remissions in patients. In contrast, success of agonistic costimulatory antibodies has thus far been limited due to insufficient induction of adaptive immune responses. Here we describe a novel vaccination method consisting of a primary dendritic cell immunization followed by a composite vaccination including an agonistic CD40 antibody, soluble antigen and a TLR3 agonist, referred to as CoAT...
February 15, 2017: Cancer Research
https://www.readbyqxmd.com/read/28201977/targeting-the-immune-niche-within-the-bone-marrow-microenvironment-the-rise-of-immunotherapy-in-multiple-myeloma
#13
Klaus Podar, D Jäger
Multiple Myeloma (MM) cells inhibit the development of an effective anti-MM immune response via defects in T cell function, ineffective antigen presentation; reduced phagocytic capacity; natural killer and dendritic cell dysfunction; decreased responsiveness to IL-2 and defects in B cell immunity; upregulation of inhibitory pathways; and production of excessive pro-inflammatory cytokines. Moreover, immune cells including plasmacytoid dendritic cells and macrophages trigger tumor cell proliferation, survival, and drug resistance...
February 13, 2017: Current Cancer Drug Targets
https://www.readbyqxmd.com/read/28197387/ciita-driven-mhc-class-ii-expressing-tumor-cells-can-efficiently-prime-naive-cd4-th-cells-in-vivo-and-vaccinate-the-host-against-parental-mhc-ii-negative-tumor-cells
#14
Farah Bou Nasser Eddine, Greta Forlani, Letizia Lombardo, Alessandra Tedeschi, Giovanna Tosi, Roberto S Accolla
Our previous studies showed that non-immunogenic H-2(d) tumor cells of distinct epithelial histotypes can become highly immunogenic, induce a protective CD4(+) T cell response and vaccinate the animals against parental MHC-II-negative cells if they are rendered MHC class II-positive by stable transfection with the Air-1-encoded MHC-II transcriptional activator CIITA. These studies did not establish, however, whether tumor immunity was the consequence of a direct priming of naive CD4(+) T lymphocytes by CIITA-driven MHC-II-expressing tumor cells or by MHC-II-tumor antigen complexes engulfed by dendritic cells (DC) and exposed on the surface of these professional antigen presenting cells (APC)...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28197373/systemic-activation-of-antigen-presenting-cells-via-rna-loaded-nanoparticles
#15
Elias J Sayour, Gabriel De Leon, Christina Pham, Adam Grippin, Hanna Kemeny, Joshua Chua, Jianping Huang, John H Sampson, Luis Sanchez-Perez, Catherine Flores, Duane A Mitchell
While RNA-pulsed dendritic cell (DC) vaccines have shown promise, the advancement of cellular therapeutics is fraught with developmental challenges. To circumvent the challenges of cellular immunotherapeutics, we developed clinically translatable nanoliposomes that can be combined with tumor-derived RNA to generate personalized tumor RNA-nanoparticles (NPs) with considerable scale-up capacity. RNA-NPs bypass MHC restriction, are amenable to central distribution, and can provide near immediate immune induction...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28194716/irradiation-enhances-dendritic-cell-potential-antitumor-activity-by-inducing-tumor-cell-expressing-tnf-%C3%AE
#16
Lijia Chang, Zhengzheng Zhang, Fang Chen, Wen Zhang, Shuang Song, Shuxia Song
Dendritic cells (DCs)-based tumor vaccines have shown to be the promising methods for inducing therapeutic antitumor response. However, DCs alone rarely carry curative antitumor activity, and the immunosuppressive microenvironment may contribute to this defect of DC vaccinal function. Irradiation in combination with DCs has been shown to promote immune-mediated tumor destruction in preclinical studies. However, little is known about how irradiation alters the tumor microenvironment, and what host pathways modulate the activity of administrated DCs...
March 2017: Medical Oncology
https://www.readbyqxmd.com/read/28193909/rv2299c-a-novel-dendritic-cell-activating-antigen-of-mycobacterium-tuberculosis-fused-esat-6-subunit-vaccine-confers-improved-and-durable-protection-against-the-hypervirulent-strain-hn878-in-mice
#17
Han-Gyu Choi, Seunga Choi, Yong Woo Back, Seungwha Paik, Hye-Soo Park, Woo Sik Kim, Hongmin Kim, Seung Bin Cha, Chul Hee Choi, Sung Jae Shin, Hwa-Jung Kim
Understanding functional interactions between DCs and antigens is necessary for achieving an optimal and desired immune response during vaccine development. Here, we identified and characterized protein Rv2299c (heat-shock protein 90 family), which effectively induced DC maturation. The Rv2299c-maturated DCs showed increased expression of surface molecules and production of proinflammatory cytokines. Rv2299c induced these effects by binding to TLR4 and stimulating the downstream MyD88-, MAPK- and NF-κB-dependent signaling pathways...
February 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/28193898/systems-analysis-of-protective-immune-responses-to-rts-s-malaria-vaccination-in-humans
#18
Dmitri Kazmin, Helder I Nakaya, Eva K Lee, Matthew J Johnson, Robbert van der Most, Robert A van den Berg, W Ripley Ballou, Erik Jongert, Ulrike Wille-Reece, Christian Ockenhouse, Alan Aderem, Daniel E Zak, Jerald Sadoff, Jenny Hendriks, Jens Wrammert, Rafi Ahmed, Bali Pulendran
RTS,S is an advanced malaria vaccine candidate and confers significant protection against Plasmodium falciparum infection in humans. Little is known about the molecular mechanisms driving vaccine immunity. Here, we applied a systems biology approach to study immune responses in subjects receiving three consecutive immunizations with RTS,S (RRR), or in those receiving two immunizations of RTS,S/AS01 following a primary immunization with adenovirus 35 (Ad35) (ARR) vector expressing circumsporozoite protein. Subsequent controlled human malaria challenge (CHMI) of the vaccinees with Plasmodium-infected mosquitoes, 3 wk after the final immunization, resulted in ∼50% protection in both groups of vaccinees...
February 13, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28191816/interferon-%C3%AE-inducible-dendritic-cells-matured-with-ok-432-exhibit-trail-and-fas-ligand-pathway-mediated-killer-activity
#19
Terutsugu Koya, Ryu Yanagisawa, Yumiko Higuchi, Kenji Sano, Shigetaka Shimodaira
Active human dendritic cells (DCs), which efficiently induce immune responses through their functions as antigen-presenting cells, exhibit direct anti-tumour killing activity in response to some pathogens and cytokines. These antigen-presenting and tumour killing abilities may provide a breakthrough in cancer immunotherapy. However, the mechanisms underlying this killer DC activity have not been fully proven, despite the establishment of interferon-α (IFN-α)-generated killer DCs (IFN-DCs). Here mature IFN-DCs (mIFN-DCs), generated from IFN-DCs primed with OK-432 (streptococcal preparation), exhibited elevated expression of CD86 and human leukocyte antigen-DR (minimum criteria for DC vaccine clinical trials) as well as antigen-presenting abilities comparable with those of mature IL-4-DCs (mIL-4-DCs)...
February 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28187172/generation-of-dendritic-cell-based-vaccine-using-high-hydrostatic-pressure-for-non-small-cell-lung-cancer-immunotherapy
#20
Nada Hradilova, Lenka Sadilkova, Ondrej Palata, Dagmar Mysikova, Hana Mrazkova, Robert Lischke, Radek Spisek, Irena Adkins
High hydrostatic pressure (HHP) induces immunogenic death of tumor cells which confer protective anti-tumor immunity in vivo. Moreover, DC pulsed with HHP-treated tumor cells induced therapeutic effect in mouse cancer model. In this study, we tested the immunogenicity, stability and T cell stimulatory activity of human monocyte-derived dendritic cell (DC)-based HHP lung cancer vaccine generated in GMP compliant serum free medium using HHP 250 MPa. DC pulsed with HHP-killed lung cancer cells and poly(I:C) enhanced DC maturation, chemotactic migration and production of pro-inflammatory cytokines after 24h...
2017: PloS One
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