Day 3 Poly (I:C)-activated dendritic cells generated in CellGro for use in cancer immunotherapy trials are fully comparable to standard Day 5 DCs

Fast dendritic cells matured with Poly (I:C) may acquire tolerogenic properties

“…Moreover, it could lead to increased tolerogenicity, especially if the co-stimulatory molecules are poorly expressed by such cells [36]. In line with this, Truxova et al [14] showed that Poly (I:C)e matured 3-day DCs express lower levels of CD80 and CD86 compared with Poly (I:C)ematured 5-day DCs, which is in accordance with our results. Another study also reported a weaker expression of CCR7 by fDCs generated by 24-h differentiation with GM-CSF/IL-4 and 24-h maturation with a proinflammatory cocktail, in comparison to the conventional DCs [17], which suggests that such cells have a weaker migratory capability [37].…”

“…Although the majority of studies concluded that fDCs are as good as their conventional counterparts [12,14e18], there is no strong evidence confirming that the fast DC protocol is efficient enough to undergo clinical trials. Namely, it has been reported that fDCs could have a weaker antigen uptake [15,16], antigen presentation and costimulation [14,16] and higher IL-10 production on stimulation with a TLR7/8 agonist [17]. Similarly, we showed previously that DCs generated by the fDC protocol mature poorly in the presence of proinflammatory cocktail, unlike their conventional counterparts [18].…”

“…Truxova et al [14] recently suggested that DCs generated with GM-CSF/IL-4 for 3 or 5 days and then stimulated for 24 h with Poly (I:C) have similar potential for DC-based vaccines. Despite having relatively high expression of CD14 and poor production of IL-12p70, this conclusion came from the observations that 3-day-and 5-day DCs have similar internalization and viral/bacterial antigen presentation capability as well as the ability to induce antigenspecific proliferation of CD8 þ T cells.…”

“…The majority of studies comparing the conventional and fast protocol suggested that fast DCs (fDCs) are as good as their conventional counterparts [12,14e17]. However, different data showing that fDCs have a weaker antigen uptake [15,16], weaker antigen presentation and co-stimulation [14,16] and a higher IL-10 production on stimulation [17] point to their weaker potential in a clinical setting for antitumor therapy. In line with this, our previous data [18] suggest that the conventional protocol for the generation of DCs is more reliable than the fast DC protocol because the monocytes of all examined donors cultivated by standard methods had good potential to differentiate into mature, IL12eproducing DCs.…”

“…Knowing that Poly (I:C) is a potent inducer of DC-mediated Th1 immune response [21,25] and that it has already been proposed as a good agent for fDC protocols [14,26], we assessed whether its application in the fDC protocol could overcome the weak response of the non-responders to the fDC differentiation protocol and whether it potentially induces tolerogenic effects that are adverse for cancer immunotherapy.…”