Furthermore, CTLs generated from v-FlaB/IFN-/TNF- DCs have great capacity to migrate to the tumor site. Our group has also investigated the effect of natural products on DC maturation and Th1 polarization. polarization (high level of IFN- and low level of IL-13 with a high level of expression of the Th1-bringing in chemokine IP-10). These DCs can generate antigen-specific IFN–secreting cells with 6-fold higher generation than with standard PGE2 DCs. Furthermore, CTLs generated from v-FlaB/IFN-/TNF- DCs have great capacity to migrate to the tumor site. Our group has also investigated the effect of natural products on DC maturation and Th1 polarization. possesses two active components, uncarinic acid C and ursolic acid, that induce potent mature DCs. Uncarinic acid C can modulate DC functions that favor a Th1 response. To get more effective DCs, the addition of IFN- to uncarinic acid C augmented CCR7 expression of DCs, IL-12p70 production from DCs, and secretion of IFN- by CTL cells.46 Ursolic acid induces IL-12p70 production on DCs in a dose-dependent manner. Use of anti-TLR2 and anti-TLR4 antibodies proved that ursolic acid can generate mature DCs through conversation with TLR2 and/or TLR4.47 Cryptomerione is classified as a terpene compound and is present in em Cryptomeria japonica /em . The presence of Cryptomerione helps to increase the IL-12p70 level and reduce the IL-10 level from cholera toxin-pulsed DCs and to promote DC migration.48 Furthermore, based on the cross-talk among DCs, NK cells, and CD8+ T lymphocytes, several DC vaccines were generated through interaction with these helper cells in combination with cytokines and TLR agonists.52,53,54 In fact, DCs help NK cells to exert tumoricidal activity and, in turn, NK cells activate DCs to induce maturation and cytokine secretion toward Th1 polarization. DC and NK cell conversation gives rise to mutual activation and cytokine production of both cells. Induction of DC maturation requires 2 signals of helper and effector NK cells. The helper signal of both cells is required by direct contact between DCs and NK cells.55 Co-culturing of immature DCs with resting or activated NK cells showed that DC maturation was promoted by resting NK cells and dependent on stimulation condition.54 2. Tumor antigens to weight onto DCs A good tumor antigen candidate should present a broad tumor-specific fingerprint, the possibility to form MHC class I-peptide complex, ease of preparation, and reduction of immune suppression. As a starting point, Id-proteins were used as a tumor antigen to pulse onto DCs and gave a good immune response in MM. However, a Lorediplon high level of Id-protein in a patient’s serum depletes the response. This reduced response led to the application of tumor-associated antigens (TAAs). Most TAAs are also expressed on normal cells at a lower level, which imposes a risk of autoimmune reaction in malignancy patients. Fortunately, several investigations have shown that the Lorediplon use of TAAs is usually feasible and safe for malignancy patients. In general, extracellular protein uptake by DCs gives rise to Th2 polarization and the uptake was poor. As a consequence, TAAs were used in peptide sequence form such that the vaccine encounters a limited anti-tumor CTL repertoire associated with certain peptide epitopes. To overcome the problem, a cocktail of peptides, whole tumor cells, and their derivatives were used instead of Lorediplon a single peptide to pulse onto DCs, which activate a Lorediplon broad tumor-specific CTL repertoire.56 Whole tumor cell lysate can be prepared through a freezing-thawing process, apoptotic bodies from ultraviolet B irradiation (UVB), tumor-derived RNA, tumor-derived Hsp, or live tumor fused with DCs. Tumor lysate of total mononuclear cells obtained from bone marrow can induce an autoimmune reaction related to healthy cells and reduce the capacity of antigen uptake by DCs. We showed that a high concentration of tumor lysates can suppress DC function and that purified CD138+ cell lysate-pulsed DCs can induce a higher CTL response than total cell lysate-pulsed DCs. In addition, DCs pulsed with an optimal concentration of purified tumor lysate could induce a potent myeloma-specific Rabbit Polyclonal to CHP2 CTL response.29 In the clinical setting, it is very difficult to get enough malignant MM cells for DC vaccine preparation. Our group investigated the possibility of DCs pulsed with allogeneic myeloma cells, prepared from an allogeneic MM cell.