Academic Journal
Synthetic Melanin Acts as Efficient Peptide Carrier in Cancer Vaccine Strategy
العنوان: | Synthetic Melanin Acts as Efficient Peptide Carrier in Cancer Vaccine Strategy |
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المؤلفون: | Cuzzubbo, Stefania, Roch, Benoit, Darrasse-Jèze, Guillaume, Hosten, Benoit, Leclercq, Manon, Vignal, Nicolas, Banissi, Claire, Tartour, Eric, Carpentier, Antoine, F |
المساهمون: | Paris-Centre de Recherche Cardiovasculaire (PARCC (UMR_S 970/ U970)), Hôpital Européen Georges Pompidou APHP (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Immunologie - Immunopathologie - Immunothérapie CHU Pitié Salpêtrière (I3), CHU Charles Foix AP-HP, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière AP-HP, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Optimisation thérapeutique en Neuropsychopharmacologie (OPTeN (UMR_S 1144 / U1144)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), G.D.-J was supported by grant PJA 20141201668 from La Fondation ARC and grant PLBIO19-075 from Institut National du Cancer (INCA). The PhD program of S.C. was financially sup- ported by Plan Cancer 2018 «Soutien pour la formation à la recherche translationnelle en cancérologie» |
المصدر: | ISSN: 1661-6596. |
بيانات النشر: | HAL CCSD MDPI |
سنة النشر: | 2022 |
مصطلحات موضوعية: | 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, Roch, Darrasse-Jèze, Hosten, Leclercq, Vignal, Banissi, Tartour, Carpentier, A.F. Synthetic melanin, L-DOPA, cancer vaccine, adjuvant, nanoparticles, carrier, delivery system, peptide vaccine, dendritic cells, Langerhans cells, melanin |
الوصف: | International audience ; 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. |
نوع الوثيقة: | article in journal/newspaper |
اللغة: | English |
Relation: | info:eu-repo/semantics/altIdentifier/pmid/36499300; hal-04059067; https://hal.science/hal-04059067; https://hal.science/hal-04059067/document; https://hal.science/hal-04059067/file/CuzzubboRochDarrasse-Je%CC%80zeCarpentier,IJMS%20DC%20and%20malenine-carrier%20vaccine%20in%20Cancer.pdf; PUBMED: 36499300; PUBMEDCENTRAL: PMC9738778 |
DOI: | 10.3390/ijms232314975 |
الاتاحة: | https://hal.science/hal-04059067 https://hal.science/hal-04059067/document https://hal.science/hal-04059067/file/CuzzubboRochDarrasse-Je%CC%80zeCarpentier,IJMS%20DC%20and%20malenine-carrier%20vaccine%20in%20Cancer.pdf https://doi.org/10.3390/ijms232314975 |
Rights: | info:eu-repo/semantics/OpenAccess |
رقم الانضمام: | edsbas.BB6C3095 |
قاعدة البيانات: | BASE |
DOI: | 10.3390/ijms232314975 |
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