Dendritic cell-based immunotherapy: a basic review and recent advances

Abstract

Dendritic cells (DCs) are considered a very promising arm to activate the immune system in immunotherapeutic strategies against cancer. DCs are the most powerful antigen-presenting cells (APCs), being highly efficient at generating robust immune responses. They are also considered the center of the immune system, since they provide a crucial link between both innate and adaptive immune responses. Thus, DC-based cancer immunotherapy aims to take advantage of these unique characteristics of DCs to better fight cancer. During the last decade, they have been the subject of numerous studies intending to develop immunotherapeutic strategies against cancer through vaccination. For this purpose, it is essential to gain a better insight into DC immunobiology, regulation of innate and adaptive immune systems, and tumor microenvironment, as well as applying the latest advances in science in order to boost their enormous anti-tumor immunotherapeutic potential. In this review, we will hold focus on DC immunobiology (from their origin, location, and special properties and distinct subsets to the innate and adaptive immunity), on the new concept of cancer immunoediting, and on the knowledge given by clinical trials using DC vaccines. Finally, future perspectives for this emerging field are highlighted.

Cell transfer‐based immunotherapies in cancer: A review

“…The viral vectors and more recently Sleeping Beauty transposon system carrying the genes harboring chimeric Ag receptors (CARs) or TCR genes specific to tumor Ags are introduced genetically into regular peripheral blood T cells for the production of CAR T cells and TCR T cells, respectively . The first generation of CARs expresses molecules resulting from the fusion of an Ag‐binding domain, in most cases single‐chain variable fragment, and an intracellular T‐cell signaling domain (CD3‐ζ), while the second and third generations of CARs also contain domains inducing costimulatory signals …”

“…There are several protocols for anticancer DC development, expansion, and maturation . There are three distinct sources for the development of DCs, two used in ex vivo protocols and one in in vivo one.…”

“…The in vivo protocol includes an extension of circulating DCs by the introduction of hematopoietic growth factors. There are also different approaches for Ag loading including peptide, protein, tumor cell, or lysates of tumor cell pulsing, transduction of DCs with tumor Ag‐expressing genes and in some cases costimulatory or cytokine‐expressing genes preferably by lentiviral vectors, and introduction of tumor‐associated Ag‐encoding mRNA …”

“…13,42,57,58 The first generation of CARs expresses molecules resulting from the fusion of an Ag-binding domain, in most cases single-chain variable fragment, and an intracellular T-cell signaling domain (CD3-ζ), while the second and third generations of CARs also contain domains inducing costimulatory signals. 59 These genetically engineered lymphocytes have a high tumor reactivity and avidity. 60 Genetically engineered T lymphocytes highly reactive to melanoma Ag recognized T cells 1 (MART-1) are associated with regression of the tumor in metastatic melanoma patients.…”

“…82 There are several protocols for anticancer DC development, expansion, and maturation. 59 There are three distinct sources for the development of DCs, two used in ex vivo protocols and one in in vivo one. In the former protocols, PBMCs and CD34 + hematopoietic precursors are extracted from the patient, the latter through leukapheresis following granulocyte-macrophage colony-stimulating factor (GM-CSF) pretreatment expanded in the presence of factors including Flt3L, GM-CSF, TNF-α, IL-1β, IL-4, and IL-6 during a period of 2-7 days, and generate mature DCs after exposure to a cocktail of maturation inducing cytokines.…”