Abstract
Recent studies reveal that Seneca Valley Virus (SVV) exploits tumor endothelial marker 8 (TEM8) for cellular entry, the same surface receptor pirated by bacterial-derived anthrax toxin. This observation is particularly significant as SVV is a known oncolytic virus which selectively infects and kills tumor cells, particularly those of neuroendocrine origin. TEM8 is a transmembrane glycoprotein that is preferentially upregulated in some tumor cell and tumor-associated stromal cell populations. Both TEM8 and SVV have been evaluated for targeting of tumors of multiple origins, but the connection between the two was previously unknown. Here, we review currently understood interactions between TEM8 and SVV, anthrax protective antigen (PA), and collagen VI, a native binding partner of TEM8, with an emphasis on potential therapeutic directions moving forward.
Highlights
A recurring hallmark in the effort to develop novel cancer treatments has been identification of biologically derived agents with anti-neoplastic activity
This review aims to provide a backdrop for ongoing research devoted to understanding tumor endothelial marker 8 (TEM8) and the interplay between TEM8 and collagen in cancer, and how two unrelated foreign biologics happen to target the same protein
small cell lung cancer (SCLC) cell lines that supported replication of Seneca Valley Virus (SVV) displayed downregulation or defects in genes related to type I interferon signaling [6]. These results suggest that additional factors, those involved with innate antiviral immunity may regulate oncolytic activity of SVV beyond cellular binding and internalization, and another report suggested a role for sialic acid in regulating SVV infection of glioblastoma [57]
Summary
A recurring hallmark in the effort to develop novel cancer treatments has been identification of biologically derived agents with anti-neoplastic activity. More recent work has focused on discovery and characterization of viruses that selectively target tumor cells—i.e., oncolytic viruses. In 2015 the first oncolytic virus, Talimogene Laherparepvec (T-VEC), a genetically modified herpesvirus, was approved for melanoma treatment [1]. Fueled by this success, new oncolytic viruses were developed for tumorspecific killing, including polioviruses targeting CD155 in brain cancers [2] and adenoviruses armed with EGFR-targeting, bispecific T-cell engagers [3]. While oncolytic viruses are being evaluated against many tumor types, better understanding of the mechanisms regulating tumor-selective tropism is needed
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