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Antitumor dendritic cell–based vaccines: lessons from 20 years of clinical trials and future perspectives

  • João Constantino
    Affiliations
    Faculty of Pharmacy and Centre for Neuroscience and Cell Biology (CNC), University of Coimbra, Coimbra, Portugal
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  • Célia Gomes
    Affiliations
    Faculty of Medicine, Laboratory of Pharmacology and Experimental Therapeutics, Institute for Biomedical Imaging and Life Sciences (IBILI) and Center of Investigation in Environment, Genetics and Oncobiology (CIMAGO), University of Coimbra, Coimbra, Portugal

    CNC.IBILI, University of Coimbra, Coimbra, Portugal
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  • Amílcar Falcão
    Affiliations
    Faculty of Pharmacy and Centre for Neuroscience and Cell Biology (CNC), University of Coimbra, Coimbra, Portugal

    CNC.IBILI, University of Coimbra, Coimbra, Portugal
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  • Maria T. Cruz
    Affiliations
    Faculty of Pharmacy and Centre for Neuroscience and Cell Biology (CNC), University of Coimbra, Coimbra, Portugal

    CNC.IBILI, University of Coimbra, Coimbra, Portugal
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  • Bruno M. Neves
    Correspondence
    Reprint requests: Bruno M. Neves, Faculty of Pharmacy and Centre for Neuroscience and Cell Biology, University of Coimbra, 3000-548 Coimbra, Portugal
    Affiliations
    Faculty of Pharmacy and Centre for Neuroscience and Cell Biology (CNC), University of Coimbra, Coimbra, Portugal

    CNC.IBILI, University of Coimbra, Coimbra, Portugal

    Department of Chemistry and QOPNA, Mass Spectrometry Centre, University of Aveiro, Aveiro, Portugal
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Published:August 03, 2015DOI:https://doi.org/10.1016/j.trsl.2015.07.008
      Dendritic cells (DCs) are versatile elements of the immune system and are best known for their unparalleled ability to initiate and modulate adaptive immune responses. During the past few decades, DCs have been the subject of numerous studies seeking new immunotherapeutic strategies against cancer. Despite the initial enthusiasm, disappointing results from early studies raised some doubts regarding the true clinical value of these approaches. However, our expanding knowledge of DC immunobiology and the definition of the optimal characteristics for antitumor immune responses have allowed a more rational development of DC-based immunotherapies in recent years. Here, after a brief overview of DC immunobiology, we sought to systematize the knowledge provided by 20 years of clinical trials, with a special emphasis on the diversity of approaches used to manipulate DCs and their consequent impact on vaccine effectiveness. We also address how new therapeutic concepts, namely the combination of DC vaccines with other anticancer therapies, are being implemented and are leveraging clinical outcomes. Finally, optimization strategies, new insights, and future perspectives on the field are also highlighted.

      Abbreviations:

      APCs (antigen-presenting cells), cDCs (classical DCs), CTLs (cytotoxic T cells), CTLA-4 (cytotoxic T-lymphocyte-associated antigen 4), DC (dendritic cell), Dex (dendritic cell–derived exosomes), EMA (European Medicines Agency), FDA (Food and Drug Administration), GM-CSF (granulocyte-macrophage colony–stimulating factor), HLA (human leukocyte antigen), HSC (hematopoietic stem cells), i.d. (intradermal), IDO (indoleamine-2,3-dioxygenase), IL (interleukin), IFN (interferon), i.n. (intranodal), iPSCs (induced pluripotent stem cells), i.t. (intratumoral), i.v. (intravenous), LC (Langerhans cells), mAb (monoclonal antibody), MAGE (melanoma-associated antigen), MDPs (macrophage and DC precursors), MDSCs (myeloid-derived suppressor cells), MHC (major histocompatibility complex), MoDCs (monocyte-derived DCs), NK (natural killer), PAP (prostatic acid phosphatase), PBMCs (peripheral blood mononuclear cells), PD-1 (programmed cell death 1), pDCs (plasmacytoid DCs), PGE2 (prostaglandin E2), Poly-I:C (polyinosinic:polycytidylic acid), Poly-ICLC (polyriboinosinic-polyribocytidylic acid-polylysine carboxymethylcellulose), s.c. (subcutaneous), SCF (stem cell factor), TAAs (tumor-associated antigens), TCR (T-lymphocyte receptor), TGF (transforming growth factor), TLR (toll-like receptor), Tregs (regulatory T cells)
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