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

Erkko Ylösmäki, Leena Ylösmäki, Manlio Fusciello, Beatriz Martins, Petra Ahokas, Hanne Cojoc, Arttu Uoti, Sara Feola, Anna Kreutzman, Tuuli Ranki, Julia Karbach, Tapani Viitala, Petri Priha, Elke Jäger, Sari Pesonen, Vincenzo Cerullo*

*Corresponding author for this work

Research output: Contribution to journalArticleScientificpeer-review

5 Citations (Scopus)

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 VALO-D102, 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.

Original languageEnglish
Pages (from-to)459-469
Number of pages11
JournalMolecular Therapy - Oncolytics
Volume20
DOIs
Publication statusPublished - 26 Mar 2021
Externally publishedYes
MoE publication typeA1 Journal article-refereed

Keywords

  • CD40L
  • oncolytic vaccine
  • OX40L
  • PeptiCRAd
  • T cell activation

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