Pre-clinical development of Listeria-based nanovaccines as immunotherapies for solid tumours: insights from melanoma

Hector Teran-Navarro, Ricardo Calderon-Gonzalez, David Salcines-Cuevas, Isabel Garcia, Marco Marradi, Javier Freire, Erwan Salmon, Mar Portillo-Gonzalez, Elisabet Frande-Cabanes, Almudena Garcia-Castaño, Virginia Martinez-Callejo, Jose Javier Gomez-Roman, Raquel Tobes, Fernando Rivera, Sonsoles Yañez-Diaz, Carmen Alvarez-Dominguez

Research output: Contribution to journalArticlepeer-review

4 Citations (Scopus)

Abstract

Gold glyconanoparticles loaded with the listeriolysin O peptide 91-99 (GNP-LLO91-99), 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-LLO91-99 nanovaccines as a novel immunotherapy for cutaneous melanoma. Studies using mouse models of subcutaneous melanoma indicated that GNP-LLO91-99 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-LLO91-99 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-LLO91-99 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-LLO91-99 nanovaccines function as immune stimulators and immune effectors and serve as safe cancer therapies, alone or in combination with other immunotherapies.
Original languageEnglish
Article numbere1541534
Number of pages12
JournalOncoImmunology
Volume8
Issue number2
DOIs
Publication statusPublished - 10 Nov 2018
Externally publishedYes

Keywords

  • Listeria
  • Melanoma
  • Nanoparticles
  • Immunotherapy
  • Therapeutic vaccination

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