Systemic treatment of xenografts with vaccinia virus GLV-1h68 reveals the immunologic facet of oncolytic therapy

doi:10.1186/1471-2164-10-301

BMC Genomics
Volume 10

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Worschech A
Chen N
Yu YA
Zhang Q
Pos Z
Weibel S
Raab V
Sabatino M
Monaco A
Liu H
Monsurró V
Buller RM
Stroncek DF
Wang E
Szalay AA
Marincola FM

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Worschech A
Chen N
Yu YA
Zhang Q
Pos Z
Weibel S
Raab V
Sabatino M
Monaco A
Liu H
Monsurró V
Buller RM
Stroncek DF
Wang E
Szalay AA
Marincola FM
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Research article

Systemic treatment of xenografts with vaccinia virus GLV-1h68 reveals the immunologic facet of oncolytic therapy

Andrea Worschech¹^,2^,3 , Nanhai Chen¹ , Yong A Yu¹ , Qian Zhang¹ , Zoltan Pos³ , Stephanie Weibel¹^,2 , Viktoria Raab¹^,2 , Marianna Sabatino³ , Alessandro Monaco³ , Hui Liu³ , Vladia Monsurró⁶ , R Mark Buller⁴ , David F Stroncek⁵ , Ena Wang³ , Aladar A Szalay¹^,2 and Francesco M Marincola³

¹Genelux Corporation, San Diego Science Center, San Diego, California, USA

²Virchow Center for Experimental Biomedicine and Institute for Biochemistry, University of Würzburg, Am Hubland, Würzburg, Germany

³Infectious Disease and Immunogenetics Section (IDIS), Department of Transfusion Medicine, Clinical Center, National Institutes of Health, Bethesda, Maryland, USA

⁴Department of Molecular Microbiology and Immunology, Saint Louis University School of Medicine, St Louis, MO, USA

⁵Cellular Processing Section, Department of Transfusion Medicine, National Institutes of Health, Bethesda, Maryland, USA

⁶Department of Pathology, Immunology Section, University of Verona Medical School, Verona, Italy

author email corresponding author email

BMC Genomics 2009, 10:301doi:10.1186/1471-2164-10-301


Published:	7 July 2009

Abstract

Background

GLV-1h68 is an attenuated recombinant vaccinia virus (VACV) that selectively colonizes established human xenografts inducing their complete regression.

Results

Here, we explored xenograft/VACV/host interactions in vivo adopting organism-specific expression arrays and tumor cell/VACV in vitro comparing VACV replication patterns. There were no clear-cut differences in vitro among responding and non-responding tumors, however, tumor rejection was associated in vivo with activation of interferon-stimulated genes (ISGs) and innate immune host's effector functions (IEFs) correlating with VACV colonization of the xenografts. These signatures precisely reproduce those observed in humans during immune-mediated tissue-specific destruction (TSD) that causes tumor or allograft rejection, autoimmunity or clearance of pathogens. We recently defined these common pathways in the "immunologic constant of rejection" hypothesis (ICR).

Conclusion

This study provides the first prospective validation of a universal mechanism associated with TSD. Thus, xenograft infection by oncolytic VACV, beyond offering a promising therapy of established cancers, may represent a reliable pre-clinical model to test therapeutic strategies aimed at modulating the central pathways leading to TSD; this information may lead to the identification of principles that could refine the treatment of cancer and chronic infection by immune stimulation or autoimmunity and allograft rejection through immune tolerance.