Virotherapy of digestive tumors with rodent parvovirus: overview and perspectives

ABSTRACT

Introduction: Toolan’s H-1 parvovirus (H-1PV) exerts a cytotoxic/oncolytic effect, predominantly mediated by its non-structural protein (NS1). This rat parvovirus is harmless, unlike other parvoviruses, and its antitumor potential may be useful to clinicians as its oncolytic action appears to be true in numerous non-digestive and digestive cancers.

Areas covered: After a brief review of parvovirus genus and biology, we summarize the proposed mechanisms to explain the cytotoxicity of H-1PV to tumors which results in dysregulation of cell transcription, cell-cycle arrest, termination of cell replication, activation of cellular stress response and induction of cell death. Viral oncolysis induces a strong tumor-specific immune response leading to the recognition and elimination of minimal residual disease. As the action of H-1PV is not limited to the digestive tract, we initially analyse studies performed in non-digestive cancers such as glioma (as the virus is able to cross the blood brain barrier), and then focused more particularly on the results in digestive cancers.

Expert opinion: Based on the results of studies showing little H-1PV toxicity to living bodies, we advocate for the use of the parvovirus in cancers such as melanoma, glioma and pancreatic ductal adenocarcinoma in addition to conventional chemotherapy.

KEYWORDS:

• Cancer virotherapy
• Glioma
• Oncolytic virus
• Pancreatic ductal adenocarcinoma
• Parvoviridae
• Toolan’s H-1 parvovirus

Article highlights

• Toolan’s H-1 virus of the rat (H-1PV) has a tropism for rapidly dividing cells such as tumor cells.

• H-1PV, as other rodent parvoviruses, has the ability to induce cell cycle arrest in permissive cells.

• Anti-neoplastic activity of H-1PV and other oncolytic viruses is not only via direct killing of the cells, but also by modulation of the production of immunoregulatory molecules.

• H-1PV appears to be a potent element among the novel therapeutic approaches against some cancers, such as melanoma, glioma, and pancreatic ductal adenocarcinoma.

• Despite excellent tolerance, H-1PV shows liver persistence. A delayed risk of complications in a clinical context of preexisting liver damage cannot be excluded. Thus, its concomitant use with an antimitotic which is also toxic to the liver must be avoided.

This box summarizes key points contained in the article.

Declaration of interest

M Aprahamian is an inventor on patent US 20130344034 ‘Parovirus Having a CpG-Enriched Genome Useful for Cancer Therapy’ and another pending US patent. The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.