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

<p>Abstract</p> <p>Background</p> <p>GLV-1h68 is an attenuated recombinant vaccinia virus (VACV) that selectively colonizes established human xenografts inducing their complete regression.</p> <p>Results</p> <p>Here, we explored xenograft/VACV/host interactions <it>in vivo </it>adopting organism-specific expression arrays and tumor cell/VACV <it>in vitro </it>comparing VACV replication patterns. There were no clear-cut differences <it>in vitro </it>among responding and non-responding tumors, however, tumor rejection was associated <it>in vivo </it>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).</p> <p>Conclusion</p> <p>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.</p>

Abstract licence: CC BY-NC-ND

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