Chapter Six - Ex vivo dendritic cell generation—A critical comparison of current approaches
Section snippets
Cytokine signals
Work on granulocyte-macrophage colony-stimulating factor (GM-CSF) inspired the early development of DC culture methods. GM-CSF was initially identified in tissue culture supernatants conditioned with lung tissue of mice following lipopolysaccharide (LPS) injection, by its ability to stimulate the differentiation of mouse bone marrow cells into macrophage and granulocyte colonies (Burgess et al., 1977; Burgess and Metcalf, 1980). This growth factor was then demonstrated to enable longer survival
Physiological signals for DC differentiation
The discovery of DC in the 1973 by Ralph Steinman of Rockefeller University, followed by their scientific elucidation by him and his worldwide acolytes, earned him the Nobel Prize in Physiology or Medicine in 2011. The title of that award is appropriate, since the medical promise it has long portended is that therapeutic marshaling of the key capability of DC, initiation of specific T cell responses to antigenic peptides can be distinguished from all man-made immune interventions, because they
Gene engineering tools
Clinical limitations exhibited by the current and dominant approaches in generating DCs, driven by use of function-skewing biomolecules such as cytokines, small molecules, inhibitors and proteins (i.e., PAMPS, DAMPS, antibodies, etc.), have generated interest in supplementary methods of generating clinically functional DCs. The ever-expanding arsenal of genetic engineering tools available for mammalian cell manipulation is inspiring innovative methods of intervening with creation, maturation
Clinical trials of DC-based vaccines
The use of DCs for immunotherapy applications has been a long-standing and tantalizing goal in the field of antigen presentation. The clinical potential for therapeutic anti-cancer vaccines with cytokine-derived mDC generated a great deal of interest and excitement for more than a decade, beginning in the mid-late 1990s, when DC vaccination was utilized in hundreds of early-stage clinical trials targeting virtually every tumor type in which a defined tumor-associated Ag (TAA), whole tumor
Concluding remarks
Since the initial discovery of DCs, years of research had provided great insights into how these professional APCs, through differential exposure of antigen, costimulatory molecules and conditioning cytokines, act as the master-switches of antigen-specific immunity or tolerance. Beginning with cytokine-generated monocyte-derived DCs, which initially provided a platform for immunobiological research, a variety of techniques have been developed to expand DCs ex vivo in large numbers with
Conflict of interest
O. S. is VP Immunology at Transimmune AG. R.L. E. has ownership interest (including patents) in, and is a consultant/advisory board member of, Transimmune, AG. No potential conflicts of interest were disclosed by the other authors.
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