Journal
MOLECULAR THERAPY-ONCOLYTICS
Volume 20, Issue -, Pages 459-469Publisher
CELL PRESS
DOI: 10.1016/j.omto.2021.02.006
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Funding
- Academy of Finland [1317206]
- ERC-Consolidator Grant [681219]
- Jane and Aatos Erkko Foundation [4705796]
- HiLIFE Fellow [797011004]
- Cancer Finnish Foundation [4706116]
- Magnus Ehrnrooth Foundation [4706235]
- Academy of Finland
- Digital Precision Cancer Medicine Flagship iCAN
- European Research Council
- European Research Council (ERC) [681219] Funding Source: European Research Council (ERC)
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Oncolytic virus therapies can enhance anti-cancer immunity by arming viruses with immunostimulatory molecules. The novel adenovirus VALOD-102 encoding CD40L and OX40L activates both innate and adaptive immune responses against tumors. In preclinical models, combination therapy with PeptiCRAd and anti-PD-1 immune checkpoint inhibitors shows promising results in controlling tumor growth.
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.
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