Intratumoral delivery of inactivated modified vaccinia virus Ankara (iMVA) induces systemic antitumor immunity via STING and Batf3-dependent dendritic cells Journal Article

   

Authors:	Dai, P.; Wang, W.; Yang, N.; Serna-Tamayo, C.; Ricca, J. M.; Zamarin, D.; Shuman, S.; Merghoub, T.; Wolchok, J. D.; Deng, L.
Article Title:	Intratumoral delivery of inactivated modified vaccinia virus Ankara (iMVA) induces systemic antitumor immunity via STING and Batf3-dependent dendritic cells
Abstract:	Advanced cancers remain a therapeutic challenge despite recent progress in targeted therapy and immunotherapy. Novel approaches are needed to alter the tumor immunosuppressive microenvironment and to facilitate the recognition of tumor antigens that leads to antitumor immunity. Poxviruses, such as modified vaccinia virus Ankara (MVA), have potential as immunotherapeutic agents. We show that infection of conventional dendritic cells (DCs) with heat- or ultraviolet-inactivated MVA leads to higher levels of interferon induction than MVA alone through the cGAS (cyclic guanosine monophosphate–adenosine monophosphate synthase)–STING cytosolic DNA-sensing pathway. Intratumoral injection of inactivated MVA (iMVA) was effective and generated adaptive antitumor immunity in murine melanoma and colon cancer models. iMVA-induced antitumor therapy was less effective in STING- or Batf3-deficient mice than in wild-type mice, indicating that both cytosolic DNA sensing and Batf3-dependent CD103+/CD8+ DCs are essential for iMVA immunotherapy. The combination of intratumoral delivery of iMVA and systemic delivery of immune checkpoint blockade generated synergistic antitumor effects in bilateral tumor implantation models as well as in a unilateral large established tumor model. Our results suggest that inactivated vaccinia virus could be used as an immunotherapeutic agent for human cancers. 2017 © The Authors.
Journal Title:	Science Immunology
Volume:	2
Issue:	11
ISSN:	2470-9468
Publisher:	Amer Assoc Advancement Science
Date Published:	2017-05-01
Start Page:	eaal1713
Language:	English
DOI:	10.1126/sciimmunol.aal1713
PUBMED:	28763795
PROVIDER:	scopus
PMCID:	PMC5559204
DOI/URL:	https://www.scopus.com/inward/record.uri?eid=2-s2.0-85039974971&doi=10.1126%2fsciimmunol.aal1713&partnerID=40&md5=392a9e39d0b9336bad7868a22a138e1c
Notes:	The MSK Cancer Center Support Grant (P30 CA008748) is acknowledge in the PDF -- Corresponding authors is MSK author: Liang Deng -- Source: Scopus

https://synapse.mskcc.org/synapse/works/has_related_data_chk/224481