OM-197-MP-AC adjuvant properties: the in vitro maturation of normal and leukemic dendritic cells in a serum-free culture model

• Published in: Immunobiology (1979) 2004, Vol.209 (1), p.67-77
• Main Authors: Véran, Julie, Mohty, Mohamad, Gaugler, Béatrice, Chiavaroli, Carlo, Olive, Daniel
• Format: Article
• Language: English
• Subjects: Adult; Aged; Cell Differentiation; Culture Media; Culture Media, Serum-Free; Cytokines - biosynthesis; Dendritic Cells - drug effects; Dendritic cells, OM-197; Female; Humans; Leukemia, Myeloid - pathology; Male; Middle Aged; Phenotype; Phospholipids - pharmacology; T-Lymphocytes - immunology; Tumor Cells, Cultured
• ISSN: 0171-2985; 1878-3279
• DOI: 10.1016/j.imbio.2004.02.003

Dendritic cells (DC) play a pivotal role in linking innate and adaptive immunity. Only mature DC are able to initiate adaptive immune responses by sensitising naive antigen-specific T cells. For clinical immunotherapeutic applications, safe and efficient clinical grade maturation factors of DC are required. Here, we investigated the impact of OM-197-MP-AC (OM-197), a synthetic lipid A analogue pseudo-dipeptide derived from amino acids linked to three fatty acid chains, on the maturation of human monocyte-derived-DC (Mo-DC) and leukemia-derived DC generated in serum-free conditions. After culture with clinical grade GM-CSF and IL-13, OM-197 at 20 μg/ml efficiently induced CD83 + Mo-DC. In comparison to immature Mo-DC that were derived by culture with GM-CSF and IL-13 only, CD40, CD80, CD86, HLA-ABC and HLA-DR molecules were up-regulated upon OM-197 or LPS treatment similarly. In MLR, OM-197-matured Mo-DC were found to be as potent stimulators as LPS-matured Mo-DC for CD4 + T cell proliferation. No significant difference in IFN- γ quantification was shown between naive CD4 + T cells stimulated by LPS- or OM-197-Mo-DC suggesting that OM-197-Mo-DC can drive naive T cells towards a Th1 response profile that was mainly independent of IL-12 secretion. Similarly, CD8 + T cells could be efficiently polarized into IFN- γ-secreting-cells by OM-197-Mo-DC, and activated polyclonal pp65-cytomegalovirus-specific CD8 + T lymphocytes. Finally, myeloid leukemic blasts were able to differentiate in vitro into mature functional DC-like cells upon OM-197 treatment in our culture model. Overall, the in vitro effects of clinical grade adjuvant OM-197, showed that it represents a potent inducer of both normal and leukemic-DC maturation, and is likely a good candidate for adjuvant immunotherapy in DC-based vaccines.