title: Oncolytic adenoviruses coated with MHC-I tumor epitopes increase the antitumor immunity and efficacy against melanoma.
abstract: The stimulation of the immune system using oncolytic adenoviruses (OAds) has attracted significant interest and several studies suggested that OAds immunogenicity might be important for their efficacy. Therefore, we developed a versatile and rapid system to adsorb tumor-specific major histocompatibility complex class I (MHC-I) peptides onto the viral surface to drive the immune response toward the tumor epitopes. By studying the model epitope SIINFEKL, we demonstrated that the peptide-coated OAd (PeptiCRAd) retains its infectivity and the cross presentation of the modified-exogenous epitope on MHC-I is not hindered. We then showed that the SIINFEKL-targeting PeptiCRAd achieves a superior antitumor efficacy and increases the percentage of antitumor CD8+T cells and mature epitope-specific dendritic cellsin vivo. PeptiCRAds loaded with clinically relevant tumor epitopes derived from tyrosinase-related protein 2 (TRP-2) and human gp100 could reduce the growth of primary-treated tumors and secondary-untreated melanomas, promoting the expansion of antigen-specific T-cell populations. Finally, we tested PeptiCRAd in humanized mice bearing human melanomas. In this model, a PeptiCRAd targeting the human melanoma-associated antigen A1 (MAGE-A1) and expressing granulocyte and macrophage colony-stimulating factor (GM-CSF) was able to eradicate established tumors and increased the human MAGE-A1-specific CD8+T cell population. Herein, we show that the immunogenicity of OAds plays a key role in their efficacy and it can be exploited to direct the immune response system toward exogenous tumor epitopes. This versatile and rapid system overcomes the immunodominance of the virus and elicits a tumor-specific immune response, making PeptiCRAd a promising approach for clinical testing.
authors.affiliation: Laboratory of Immunovirotherapy, Division of Pharmaceutical Biosciences and Center for Drug Research, University of Helsinki , Viikinkaari 5 , Helsinki, Finland.
authors.forename: Cristian
authors.initials: C
authors.lastname: Capasso
authors.affiliation: Laboratory of Immunovirotherapy, Division of Pharmaceutical Biosciences and Center for Drug Research, University of Helsinki , Viikinkaari 5 , Helsinki, Finland.
authors.forename: Mari
authors.initials: M
authors.lastname: Hirvinen
authors.affiliation: Laboratory of Immunovirotherapy, Division of Pharmaceutical Biosciences and Center for Drug Research, University of Helsinki, Viikinkaari 5, Helsinki, Finland; Department of Molecular Medicine and Medical Biotechnology, University of Naples "Federico II", Via Pansini, Naples, Italy.
authors.forename: Mariangela
authors.initials: M
authors.lastname: Garofalo
authors.affiliation: Laboratory of Immunovirotherapy, Division of Pharmaceutical Biosciences and Center for Drug Research, University of Helsinki , Viikinkaari 5 , Helsinki, Finland.
authors.forename: Dmitrii
authors.initials: D
authors.lastname: Romaniuk
authors.affiliation: Laboratory of Immunovirotherapy, Division of Pharmaceutical Biosciences and Center for Drug Research, University of Helsinki , Viikinkaari 5 , Helsinki, Finland.
authors.forename: Lukasz
authors.initials: L
authors.lastname: Kuryk
authors.affiliation: Laboratory of Immunovirotherapy, Division of Pharmaceutical Biosciences and Center for Drug Research, University of Helsinki , Viikinkaari 5 , Helsinki, Finland.
authors.forename: Teea
authors.initials: T
authors.lastname: Sarvela
authors.affiliation: Department of Movement Sciences and Wellness (DiSMEB), University of Naples Parthenope, Via Medina 40, Naples, Italy, CEINGE-Biotecnologie Avanzate , Via G. Salvatore 486 , Naples, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Vitale
authors.affiliation: Division of Pharmaceutical Biosciences and Center for Drug Research, University of Helsinki , Viikinkaari 5 , Helsinki, Finland.
authors.forename: Maxim
authors.initials: M
authors.lastname: Antopolsky
authors.affiliation: Division of Pharmaceutical Biosciences and Center for Drug Research, University of Helsinki , Viikinkaari 5 , Helsinki, Finland.
authors.forename: Aniket
authors.initials: A
authors.lastname: Magarkar
authors.affiliation: Division of Pharmaceutical Biosciences and Center for Drug Research, University of Helsinki , Viikinkaari 5 , Helsinki, Finland.
authors.forename: Tapani
authors.initials: T
authors.lastname: Viitala
authors.affiliation: Division of Pharmaceutical Biosciences and Center for Drug Research, University of Helsinki , Viikinkaari 5 , Helsinki, Finland.
authors.forename: Teemu
authors.initials: T
authors.lastname: Suutari
authors.affiliation: Division of Pharmaceutical Biosciences and Center for Drug Research, University of Helsinki , Viikinkaari 5 , Helsinki, Finland.
authors.forename: Alex
authors.initials: A
authors.lastname: Bunker
authors.affiliation: Division of Pharmaceutical Biosciences and Center for Drug Research, University of Helsinki , Viikinkaari 5 , Helsinki, Finland.
authors.forename: Marjo
authors.initials: M
authors.lastname: Yliperttula
authors.affiliation: Division of Pharmaceutical Biosciences and Center for Drug Research, University of Helsinki, Viikinkaari 5, Helsinki, Finland; School of Pharmacy, University of Eastern Finland, Yliopistonranta 1, Kuopio, Finland.
authors.forename: Arto
authors.initials: A
authors.lastname: Urtti
authors.affiliation: Laboratory of Immunovirotherapy, Division of Pharmaceutical Biosciences and Center for Drug Research, University of Helsinki , Viikinkaari 5 , Helsinki, Finland.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Cerullo
keywords: Cancer vaccine; humanized mice; immunotherapy; melanoma; oncolytic adenovirus; oncolytic vaccine; tumor epitopes