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      Trial watch : Dendritic cell-based interventions for cancer therapy

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          Abstract

          Dendritic cells (DCs) occupy a central position in the immune system, orchestrating a wide repertoire of responses that span from the development of self-tolerance to the elicitation of potent cellular and humoral immunity. Accordingly, DCs are involved in the etiology of conditions as diverse as infectious diseases, allergic and autoimmune disorders, graft rejection and cancer. During the last decade, several methods have been developed to load DCs with tumor-associated antigens, ex vivo or in vivo, in the attempt to use them as therapeutic anticancer vaccines that would elicit clinically relevant immune responses. While this has not always been the case, several clinical studies have demonstrated that DC-based anticancer vaccines are capable of activating tumor-specific immune responses that increase overall survival, at least in a subset of patients. In 2010, this branch of clinical research has culminated with the approval by FDA of a DC-based therapeutic vaccine (sipuleucel-T, Provenge ®) for use in patients with asymptomatic or minimally symptomatic metastatic hormone-refractory prostate cancer. Intense research efforts are currently dedicated to the identification of the immunological features of patients that best respond to DC-based anticancer vaccines. This knowledge may indeed lead to personalized combination strategies that would extend the benefit of DC-based immunotherapy to a larger patient population. In addition, widespread enthusiasm has been generated by the results of the first clinical trials based on in vivo DC targeting, an approach that holds great promises for the future of DC-based immunotherapy. In this Trial Watch, we will summarize the results of recently completed clinical trials and discuss the progress of ongoing studies that have evaluated/are evaluating DC-based interventions for cancer therapy.

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          Taking dendritic cells into medicine.

          Dendritic cells (DCs) orchestrate a repertoire of immune responses that bring about resistance to infection and silencing or tolerance to self. In the settings of infection and cancer, microbes and tumours can exploit DCs to evade immunity, but DCs also can generate resistance, a capacity that is readily enhanced with DC-targeted vaccines. During allergy, autoimmunity and transplant rejection, DCs instigate unwanted responses that cause disease, but, again, DCs can be harnessed to silence these conditions with novel therapies. Here we present some medical implications of DC biology that account for illness and provide opportunities for prevention and therapy.
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            Decisions about dendritic cells: past, present, and future.

            A properly functioning adaptive immune system signifies the best features of life. It is diverse beyond compare, tolerant without fail, and capable of behaving appropriately with a myriad of infections and other challenges. Dendritic cells are required to explain how this remarkable system is energized and directed. I frame this article in terms of the major decisions that my colleagues and I have made in dendritic cell science and some of the guiding themes at the time the decisions were made. As a result of progress worldwide, there is now evidence of a central role for dendritic cells in initiating antigen-specific immunity and tolerance. The in vivo distribution and development of a previously unrecognized white cell lineage is better understood, as is the importance of dendritic cell maturation to link innate and adaptive immunity in response to many stimuli. Our current focus is on antigen uptake receptors on dendritic cells. These receptors enable experiments involving selective targeting of antigens in situ and new approaches to vaccine design in preclinical and clinical systems.
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              Differential antigen processing by dendritic cell subsets in vivo.

              Dendritic cells (DCs) process and present self and foreign antigens to induce tolerance or immunity. In vitro models suggest that induction of immunity is controlled by regulating the presentation of antigen, but little is known about how DCs control antigen presentation in vivo. To examine antigen processing and presentation in vivo, we specifically targeted antigens to two major subsets of DCs by using chimeric monoclonal antibodies. Unlike CD8+ DCs that express the cell surface protein CD205, CD8- DCs, which are positive for the 33D1 antigen, are specialized for presentation on major histocompatibility complex (MHC) class II. This difference in antigen processing is intrinsic to the DC subsets and is associated with increased expression of proteins involved in MHC processing.
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                Author and article information

                Journal
                Oncoimmunology
                Oncoimmunology
                ONCI
                Oncoimmunology
                Landes Bioscience
                2162-4011
                2162-402X
                01 October 2012
                01 October 2012
                : 1
                : 7
                : 1111-1134
                Affiliations
                [1 ]Université Paris Descartes/Paris V; Sorbonne Paris Cité; Paris, France
                [2 ]Institut Gustave Roussy; Villejuif, France
                [3 ]Université Paris-Sud/Paris XI; Paris, France
                [4 ]INSERM, U848; Villejuif, France
                [5 ]INSERM, U872; Paris, France
                [6 ]Centre de Recherche des Cordeliers; Paris, France
                [7 ]Pôle de Biologie, Hôpital Européen Georges Pompidou; Paris, France
                [8 ]Université Pierre et Marie Curie/Paris VI; Paris, France
                [9 ]Pôle de Biologie; Hôpital Européen Georges Pompidou; Paris, France
                [10 ]INSERM, U970; Paris, France
                [11 ]INSERM, U1015; CICBT507; Villejuif, France
                [12 ]Metabolomics Platform, Institut Gustave Roussy; Villejuif, France
                Author notes
                [†]

                These authors contributed equally to this article

                [* ]Correspondence to: Guido Kroemer, Email: kroemer@ 123456orange.fr
                Article
                2012ONCOIMM0240 21494
                10.4161/onci.21494
                3494625
                23170259
                85bdbd09-edc0-4787-aa51-42b5704dcb0f
                Copyright © 2012 Landes Bioscience

                This is an open-access article licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported License. The article may be redistributed, reproduced, and reused for non-commercial purposes, provided the original source is properly cited.

                History
                Categories
                Review

                Immunology
                immunotherapy,antigen-presenting cells,toll-like receptors,cd8+ cytotoxic t lymphocytes,provenge®,pulsed dendritic cells

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