Synthetic Melanin Acts as Efficient Peptide Carrier in Cancer Vaccine Strategy
Résumé
We previously reported that a novel peptide vaccine platform, based on synthetic melanin nanoaggregates, triggers strong cytotoxic immune responses and significantly suppresses tumor growth in mice. However, the mechanisms underlying such an efficacy remained poorly described. Herein, we investigated the role of dendritic cells (DCs) in presenting the antigen embedded in the vaccine formulation, as well as the potential stimulatory effect of melanin upon these cells, in vitro by coculture experiments and ELISA/flow cytometry analysis. The vaccine efficiency was evaluated in FLT3-L−/− mice constitutively deficient in DC1, DC2, and pDCs, in Zbtb46DTR chimera mice deficient in DC1 and DC2, and in LangerinDTR mice deficient in dermal DC1 and Langerhans cells. We concluded that DCs, and especially migratory conventional type 1 dendritic cells, seem crucial for mounting the immune response after melanin-based vaccination. We also assessed the protective effect of L-DOPA melanin on peptides from enzymatic digestion, as well as the biodistribution of melanin–peptide nanoaggregates, after subcutaneous injection using [18F]MEL050 PET imaging in mice. L-DOPA melanin proved to act as an efficient carrier for peptides by fully protecting them from enzymatic degradation. L-DOPA melanin did not display any direct stimulatory effects on dendritic cells in vitro. Using PET imaging, we detected melanin–peptide nanoaggregates up to three weeks after subcutaneous injections within the secondary lymphoid tissues, which could explain the sustained immune response observed (up to 4 months) with this vaccine technology.
Mots clés
Cuzzubbo
S. Roch
B. Darrasse-Jèze
G. Hosten
B. Leclercq
M. Vignal
N. Banissi
C. Tartour
E. Carpentier
A.F. Synthetic melanin L-DOPA cancer vaccine adjuvant nanoparticles carrier delivery system peptide vaccine dendritic cells Langerhans cells
S.
Roch
B.
Darrasse-Jèze
G.
Hosten
Leclercq
M.
Vignal
N.
Banissi
C.
Tartour
E.
Carpentier
A.F. Synthetic melanin
L-DOPA
cancer vaccine
adjuvant
nanoparticles
carrier
delivery system
peptide vaccine
dendritic cells
Langerhans cells
melanin
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