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


CONCLUSIONS
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.
Worschech
Andrea
A
Genelux Corporation, San Diego Science Center, San Diego, California, USA. worschecha@mail.nih.gov
Chen
Nanhai
N
Yu
Yong A
YA
Zhang
Qian
Q
Pos
Zoltan
Z
Weibel
Stephanie
S
Raab
Viktoria
V
Sabatino
Marianna
M
Monaco
Alessandro
A
Liu
Hui
H
Monsurró
Vladia
V
Buller
R Mark
RM
Stroncek
David F
DF
Wang
Ena
E
Szalay
Aladar A
AA
Marincola
Francesco M
FM
D000818:Animals; D045744:Cell Line, Tumor; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D020411:Oligonucleotide Array Sequence Analysis; D050130:Oncolytic Virotherapy; D050504:Oncolytic Viruses / Q000276:immunology*; D017422:Sequence Analysis, DNA; D014616:Vaccinia virus / Q000276:immunology*; D023041:Xenograft Model Antitumor Assays