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

• Published in: Translational research : the journal of laboratory and clinical medicine Vol. 168; pp. 74 - 95
• Main Authors: Constantino, João, Gomes, Célia, Falcão, Amílcar, Cruz, Maria T., Neves, Bruno M.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.02.2016
• Subjects: Animals; Cancer Vaccines - immunology; Dendritic Cells - immunology; Humans; Internal Medicine; Neoplasms - prevention & control; FDA; TCR; CTLs; MHC; Poly-I:C; IFN; iPSCs; MAGE; GM-CSF; IDO; pDCs; EMA; TAAs; HSC; CTLA-4; TLR; i.d; MDPs; APCs; PGE2; MoDCs; IL; Tregs; i.n; s.c; PBMCs; i.t; Poly-ICLC; mAb; i.v; MDSCs; TGF; Dex; LC; SCF; HLA; NK; PD-1; PAP; cDCs; DC; tumor-associated antigens; programmed cell death 1; major histocompatibility complex; polyinosinic:polycytidylic acid; subcutaneous; natural killer; macrophage and DC precursors; prostaglandin E2; monocyte-derived DCs; cytotoxic T cells; classical DCs; cytotoxic T-lymphocyte-associated antigen 4; Food and Drug Administration; dendritic cell–derived exosomes; antigen-presenting cells; human leukocyte antigen; prostatic acid phosphatase; plasmacytoid DCs; regulatory T cells; Langerhans cells; induced pluripotent stem cells; dendritic cell; indoleamine-2,3-dioxygenase; T-lymphocyte receptor; intranodal; intradermal; intravenous; interleukin; intratumoral; peripheral blood mononuclear cells; melanoma-associated antigen; stem cell factor; granulocyte-macrophage colony–stimulating factor; interferon; myeloid-derived suppressor cells; polyriboinosinic-polyribocytidylic acid-polylysine carboxymethylcellulose; toll-like receptor; hematopoietic stem cells; monoclonal antibody; transforming growth factor; European Medicines Agency
• ISSN: 1931-5244; 1878-1810
• DOI: 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.