Dendritic cells (DC) are key players in the initiation of immune responses. This cell type constitutes the most potent antigen-presenting cell, endowed with the unique capacity to cluster naïve T cells. Consequently, it has been proposed as a natural adjuvant, aiming at the triggering of T-cell responses against poor immunogens, such as tumor-associated Ag (TAA). The realization of clinical trials has long been impaired by the low frequency of circulating DC available in the blood. The development of methods of generating large numbers of DC from hemapoietic precursors has recently allowed the initiation of pioneer clinical trials. These trials have yielded promising results for cancer therapy.
Dendritic cells (DC) represent a major class of antigen-presenting cells characterized by their unique ability to prime naive T cells1. Recent works demonstrated the existence of several DC subsets which differentiate from either lymphoid or myeloid bone marrow progenitors2;3. A critical factor for myeloid DC development is granulocyte-macrophage colony-stimulating-factor (GM-CSF)4;5 whereas lymphoid DC are dependent on interleukin (IL)-3 for their survival6;7. On the basis of the expression of myeloid markers (i.e. CD11c) or IL-3 receptor-α (IL-3Rα) chain (CD123) expression, two types of DC precursors have been isolated from human peripheral blood7. One subtype displays myeloid surface markers and low levels of IL-3Rα, whereas another subtype of putative lymphoid origin express IL-3Rα, is exquisitely dependent on IL-3 for its survival and is a strong producer of type I interferons (IFNs).
Human myeloid DC can be easily generated in vitro by culturing monocytes in presence of GM-CSF and IL-44;5 whereas the so-called lymphoid DC have been obtained by isolation of precursors from blood or lymph nodes6;7.
The GM-CSF/IL4 DC have been used in clinical trials in cell therapy44. However, using these conditions, only 67% of immunized patients showed an increase in response to the treatment. Therefore it is important to improve the method, conditions or substances to improve the efficacity of the treatment.
USPTO Backgrounds
USPTO Backgrounds