Characterization of a novel OX40 ligand and CD40 ligand-expressing oncolytic adenovirus used in the PeptiCRAd cancer vaccine platform

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Ylösmäki , E , Ylösmäki , L , Fusciello , M , Martins , B , Ahokas , P , Cojoc , H , Uoti , A , Feola , S , Kreutzman , A , Ranki , T , Karbach , J , Viitala , T , Priha , P , Jäger , E , Pesonen , S & Cerullo , V 2021 , ' Characterization of a novel OX40 ligand and CD40 ligand-expressing oncolytic adenovirus used in the PeptiCRAd cancer vaccine platform ' , Molecular Therapy - Oncolytics , vol. 20 , pp. 459-469 . https://doi.org/10.1016/j.omto.2021.02.006

Title: Characterization of a novel OX40 ligand and CD40 ligand-expressing oncolytic adenovirus used in the PeptiCRAd cancer vaccine platform
Author: Ylösmäki, Erkko; Ylösmäki, Leena; Fusciello, Manlio; Martins, Beatriz; Ahokas, Petra; Cojoc, Hanne; Uoti, Arttu; Feola, Sara; Kreutzman, Anna; Ranki, Tuuli; Karbach, Julia; Viitala, Tapani; Priha, Petri; Jäger, Elke; Pesonen, Sari; Cerullo, Vincenzo
Contributor organization: Division of Pharmaceutical Biosciences
ImmunoViroTherapy Lab
Drug Research Program
TRIMM - Translational Immunology Research Program
Divisions of Faculty of Pharmacy
Division of Pharmaceutical Chemistry and Technology
Pharmaceutical biophysics group
Digital Precision Cancer Medicine (iCAN)
Date: 2021-03-26
Language: eng
Number of pages: 11
Belongs to series: Molecular Therapy - Oncolytics
ISSN: 2372-7705
DOI: https://doi.org/10.1016/j.omto.2021.02.006
URI: http://hdl.handle.net/10138/329310
Abstract: Oncolytic viruses (OVs) have been shown to induce anti-cancer immunity and enhance cancer immunotherapies, such as immune checkpoint inhibitor therapies. OV therapies can be further improved by arming OVs with immunostimulatory molecules, including various cytokines or chemokines. Here, we have developed a novel adenovirus encoding two immunostimulatory molecules: cluster of differentiation 40 ligand (CD40L) and tumor necrosis factor receptor superfamily member 4 ligand (OX40L). This novel virus, designated VALOD-102, is designed to activate both innate and adaptive immune responses against tumors. CD40L affects the innate side by licensing antigen-presenting cells to drive CD8(+) T cell responses, and OX40L increases clonal expansion and survival of CD8(+) T cells and formation of a larger pool of memory T cells. VALO-D102 and its murine surrogate VALO-mD901, expressing murine OX40L and CD40L, were used in our previously developed PeptiCRAd cancer vaccine platform. Intratumoral administration of PeptiCRAd significantly increased tumor-specific T cell responses, reduced tumor growth, and induced systemic anti-cancer immunity in two mouse models of melanoma. In addition, PeptiCRAd therapy, in combination with anti-PD-1 immune checkpoint inhibitor therapy, significantly improved tumor growth control as compared to either monotherapy alone.
Subject: 317 Pharmacy
3122 Cancers
Peer reviewed: Yes
Rights: cc_by
Usage restriction: openAccess
Self-archived version: publishedVersion


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