Dendritic cells (DC) are essential for the generation of primary adaptive immune responses, but their full immunostimulatory capacities are only reached upon maturation. The authors compared several clinical-grade adjuvants of bacterial origin to determine their ability to induce phenotypic and functional maturation of monocyte-derived DC (Dendritophages, Dphi; IDM, Paris, France) differentiated with
granulocyte-macrophage colony-stimulating factor and
interleukin-13 in single-use cell processors (VacCell; IDM, Paris, France).
Monophosphoryl lipid A, Mycobacterium bovis bacillus Calmette-Guerin, and
Ribomunyl (Pierre Fabre Medicament, Boulogne, France) all appeared able to provide the signal necessary to initiate Dphi maturation. However, only
Ribomunyl (Pierre Fabre Medicament) (containing membrane and ribosomal fractions from four bacterial strains) allowed the authors to obtain a significant enhancement of allostimulatory abilities and
cytokine production by Dphi in the absence of active cellular
infection. Addition of
interferon-gamma (IFN-gamma) to
Ribomunyl resulted in more pronounced upregulation of CD83, major histocompatibility complex class I, and
B7 molecules by Dphi. Moreover, the IFN-gamma addition modulated their
cytokine secretion, allowing higher levels of bioactive
interleukin-12 concomitant with lower levels of
interleukin-10. In kinetic studies, Dphi contact with
Ribomunyl and IFN-gamma for 6 hours was sufficient to trigger a maturation process that completed spontaneously. Thus,
Ribomunyl in association with IFN-gamma represents a suitable agent for the ex vivo production of mature monocyte-derived DC that can be used as cellular
vaccines to promote a potent type I immune response.