Pre-clinical development of

Autor: Hector, Terán-Navarro, Ricardo, Calderon-Gonzalez, David, Salcines-Cuevas, Isabel, García, Marco, Marradi, Javier, Freire, Erwan, Salmon, Mar, Portillo-Gonzalez, Elisabet, Frande-Cabanes, Almudena, García-Castaño, Virginia, Martinez-Callejo, Javier, Gomez-Roman, Raquel, Tobes, Fernando, Rivera, Sonsoles, Yañez-Diaz, Carmen, Álvarez-Domínguez
Rok vydání: 2018
Předmět:
Zdroj: Oncoimmunology. 8(2)
ISSN: 2162-4011
Popis: Gold glyconanoparticles loaded with the listeriolysin O peptide 91–99 (GNP-LLO(91-99)), a bacterial peptide with anti-metastatic properties, are vaccine delivery platforms facilitating immune cell targeting and increasing antigen loading. Here, we present proof of concept analyses for the consideration of GNP-LLO(91-99) nanovaccines as a novel immunotherapy for cutaneous melanoma. Studies using mouse models of subcutaneous melanoma indicated that GNP-LLO(91-99) nanovaccines recruite and modulate dendritic cell (DC) function within the tumour, alter tumour immunotolerance inducing melanoma-specific cytotoxic T cells, cause complete remission and improve survival. GNP-LLO(91-99) nanovaccines showed superior tumour regression and survival benefits, when combined with anti-PD-1 or anti-CTLA-4 checkpoint inhibitors, resulting in an improvement in the efficacy of these immunotherapies. Studies on monocyte-derived DCs from patients with stage IA, IB or IIIB melanoma confirmed the ability of GNP-LLO(91-99) nanovaccines to complement the action of checkpoint inhibitors, by not only reducing the expression of cell-death markers on DCs, but also potentiating DC antigen-presentation. We propose that GNP-LLO(91-99) nanovaccines function as immune stimulators and immune effectors and serve as safe cancer therapies, alone or in combination with other immunotherapies.
Databáze: OpenAIRE