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Novel method to create personalized immunotherapy treatments
August 06, 2008
Argos Therapeutics and Université de Montréal today announced the presentation of new information on Argos'process for developing dendritic cell-based immunotherapies for HIV. Results from the study demonstrate that loading monocyte-derived dendritic cells with combinations of HIV antigen RNA stimulates the expansion of HIV-specific T cells, which attack and kill HIV-infected cells. Argos' immunotherapies are generated by the Company's Arcelis™ technology, which is a platform for creating autologous, RNA-loaded dendritic cell-based therapies perfectly matched to each patient's unique virus. These data were presented in an oral poster discussion August 5, 2008 at the XVII International AIDS Conference in Mexico City. "A key step in the durable control of HIV infection requires enhancing the development of memory immune responses and the stimulation of potent cytotoxic T cells through therapeutic vaccination," said Charles Nicolette, Ph.D., Chief Scientific Officer of Argos. "Working with our colleagues at the Université de Montréal, we have shown that Argos' approach of transfecting dendritic cells with autologous, HIV-specific antigens effectively activates dendritic cells and enhances the HIV-specific T cell response. We believe that these results support our methods of developing potent immunotherapies that help patients' immune systems more effectively fight HIV infection." The inability of the immune system to effectively mount a response against HIV may be caused by a defect in the maturation of T cell memory. To explore this hypothesis, researchers from Dr. Rafick-Pierre Sékaly's laboratory at the Université de Montréal and Argos tested whether modified dendritic cells, derived from monocytes of HIV-infected individuals, could correct the defective maturation of HIV-specific CD8 T-cells responsible for virus eradication. To potentially improve the magnitude and quality of the anti-HIV T-cell response, maturing dendritic cells were transfected with mRNA-encoding autologous HIV sequences combined with mRNA encoding immune modulatory molecules. These modified dendritic cells were then tested for their ability to expand and mature T cell responses in vitro. The results of these recent assessments, presented for the first time at the International AIDS Conference in Mexico, show that this novel product induces greater proliferation, maturation and differentiation of HIV-specific CD8 cells in vitro. These properties, especially expanding memory cells, required for long term protection against pathogens, may represent an improvement worthy of future of clinical development. "We believe that this improvement may represent a significant step forward," said Dr. Sékaly, professor of immunology at the Université de Montréal. "The fact that we can stimulate a specific, long-term immune response gives us great hope that, with additional development, we will be able to give people infected with HIV a new option to battle the virus." University of Montreal

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Dendritic Cells in Cancer
by Michael R. Shurin (Editor), Russell D. Salter (Editor)
It covers all aspects of DC generation, function, survival and antitumor activity in the tumor environment both in vivo and in experimental in vitro systems. The goal in focusing on a spectrum of issues related to DC in cancer is to provide an extensive and expansive review rather than a collection of independent analyses from different authors. Specific topics to be covered include analysis of DC behavior in the tumor microenvironment, including endogenous and exogenous DC, multiple DC populations, molecular pathways responsible for DC dysfunction, tumor-derived factors altering DC polarization and activation, mechanisms of DC alterations, and the role of DC in tumor escape from immune recognition and elimination. Furthermore, additional chapters provide extensive analysis of the...
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Macrophages and Dendritic Cells: Methods and Protocols (Methods in Molecular Biology)
by Neil E. Reiner (Editor)
In light of the critical contributions of macrophages and dendritic cells to diverse inflammatory diseases and to immunity and host defense, state-of-the-art approaches to the investigation of their behavior are essential. In Macrophages and Dendritic Cells: Methods and Protocols, expert researchers contribute laboratory protocols involving these two vital cell types functioning at the junction of the innate and acquired immune systems. The volume delves first into isolation and cell culturing then continues with topics such as phagocytosis, genetic manipulation, macrophage activation, and lipid signaling. Written in the highly successful Methods in Molecular Biology™ series format, chapters include brief introductions to their respective subjects, lists of the necessary materials and...
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The Biology of Dendritic Cells and HIV Infection
by Sandra Gessani (Editor), Filippo Belardelli (Editor)
Dendritic cells play the most vital part in inducing anti-viral immune responses in HIV and AIDS among many other viruses. Research on dendritic cells (DCs) is emerging as a fundamental aspect for the comprehension of the mechanisms underlying the pathogenesis of viral diseases. This volume focuses on the role of DCs in the pathogenesis and immunity of HIV-1 infection. It is the only comprehensive volume on pathogenesis and immunity of Dendritic Cells that also focuses on HIV.
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Dendritic Cell Interactions with Bacteria (Advances in Molecular and Cellular Microbiology)
by Maria Rescigno (Editor)
Emerging evidence suggests that dendritic cells play a major role in the orchestration of the immune response to bacteria. This volume introduces the reader to the complex world of dendritic cells and describes how the intimate interplay between dendritic cells, bacteria and the environment dictates either the induction of immunity or tolerance to the encountered microorganisms. It discusses how this can allow organisms to tolerate beneficial bacteria and to react against pathogens, as well as the strategies pathogenic bacteria have evolved to escape dendritic cell patrolling. Expert contributors discuss everything from bacterial capture and recognition to their killing, processing and the induction of adaptive immunity. Particular focus is on the tissue context in which bacteria are...
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Lung Macrophages and Dendritic Cells in Health and Disease (Lung Biology in Health and Disease)
by Mary Lipscomb (Editor)
Presenting the most recent findings by nearly 50 internationally established researchers, this critical reference elucidates the pivotal role of macrophages and dendritic cells (DCs) in lung homeostasis, immune regulation, and effective therapy for respiratory tract infections. Examines important molecular biological mechanisms with the aid of numerous easy-to-follow diagrams.
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Dendritic Cells: Types, Life Cycles and Biological Functions (Cell Biology Research Progress)
by Lorraine C. Welles (Editor)
Dendritic cells (DCs) are professional antigen presenting cells (APCs) that were discovered several decades ago. They play a crucial role in the innate and adaptive immune response against bacteria or viruses. This book reviews research in the field of dendritic cells including a review of the recent progress in understanding the correlation between the approach used to obtain dendritic cells and their related properties, in order to indicate a correct application of DCs for research or clinical studies.
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Handbook of Dendritic Cells: Biology, Diseases and Therapies (3 Volume )
by Manfred B. Lutz (Editor), Nikolaus Romani (Editor), Alexander Steinkasserer (Editor), Ralph M. Steinman (Editor)
This is the most comprehensive handbook on dendritic cells, featuring an introduction by Ralph M. Steinman and written by top experts. In three volumes, it covers all aspects from molecular cell biology to clinical applications, highlighting the role of dendritic cells in fighting cancer, virus infections, and autoimmune diseases. The first section on cell biology looks at dendritic cell development, circulating cells, T cell priming, Th1 and Th2 decision and CTL priming. A second part on dendritic cells in disease deals with parasites, bacteria, viruses, autoimmunity, allergies, asthma and cancer. The final section on therapeutic applications includes viral infections and antigen delivery.
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Footmarks of Innate Immunity in the Ovary and Cytokeratin-Positive Cells as Potential Dendritic Cells (Advances in Anatomy, Embryology and Cell Biology)
by Katharina Spanel-Borowski (Author)
The monograph introduces innate immunity as second authority in the ovary besides the endocrine system. Innate immunity appears to orchestrate follicular atresia, follicle rupture, follicle transformation into a corpus luteum (CL) and CL regression through nonsterile inflammation and tissue repair. The concept is new. It centres on cytokeratin-positive (CK+) cells being recognized as a potential nonlymphoid dendritic cell type (DC). Part I describes morphological aspects of immune privilege starting with active hamster ovary implants into the chicken chorioallantois membrane. Follicular atresia and follicle rupture correspond with mild and moderate tissue damage in ovaries of small rodents and rabbits. Superovulations cause severe tissue damage through intraovarian oocyte release with...
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Dendritic Cells and Virus Infection (Current Topics in Microbiology and Immunology)
by Alexander Steinkasserer (Editor)
Dendritic cells are vital to induce potent anti-viral immune responses. It will become clear to the reader that dendritic cells often play a dual role during viral infections. On the one hand they are able to mount potent antiviral immune responses, and on the other hand several viruses, including HIV-1, use DC as a vector to be transferred from the periphery to the lymph nodes where they infect their prime target.
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Dendritic Cells (Handbook of Experimental Pharmacology)
by Giovanna Lombardi (Editor), Yanira Riffo-Vasquez (Editor)
This book provides in the first part an overview of dendritic cell (DC) biology and the role of DCs in some human diseases. The second part of the book illustrates some of the way that DCs can be manipulated for immunotherapy to either induce tolerance in autoimmunity and transplantation or enhance the immune responses such as in infection or cancer.
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