Abstract
Oncolytic virotherapy of cancer is among the innovative modalities being under development and especially promising for targeting tumors, which are resistant to conventional treatments. Presently, at least a dozen of viruses, belonging to nine different virus families, are being tested within the frames of various clinical studies in cancer patients. Continuously growing preclinical evidence showing that the autonomous rat parvovirus H-1 (H-1PV) is able to kill tumor cells that resist conventional treatments and to achieve a complete cure of various human tumors in animal models argues for its inclusion in the arsenal of oncolytic viruses with an especially promising bench to bedside translation potential. Oncolytic parvovirus safe administration to humans relies on the intrinsic preference of these agents for quickly proliferating, metabolically, and biochemically disturbed tumor versus normal cells (tumor selectivity or oncotropism). The present review summarizes and discusses (i) preclinical evidence of H-1PV innocuousness for normal cells and healthy tissues in vitro and in animals, respectively, (ii) toxicological assessments of H-1PV mono- or combined therapy in tumor-bearing virus-permissive animal models, as well as (iii) historical results of experimental infection of human cancer patients with H-1PV. Altogether, these data argue against a risk of H-1PV inducing significant toxic effects in human patients. This highly favorable safety profile allowed the translation of H-1PV preclinical research into a Phase I/IIa clinical trial being currently in progress.
Highlights
Specialty section: This article was submitted to Biosafety and Biosecurity, a section of the journal Frontiers in Bioengineering and Biotechnology
Oncolytic virotherapy of cancer is among the innovative modalities being under development and especially promising for targeting tumors, which are resistant to conventional treatments
Growing preclinical evidence showing that the autonomous rat parvovirus H-1 (H-1PV) is able to kill tumor cells that resist conventional treatments and to achieve a complete cure of various human tumors in animal models argues for its inclusion in the arsenal of oncolytic viruses with an especially promising bench to bedside translation potential
Summary
Oncolytic virotherapy is one of the innovative modalities under development to target tumors that are refractory to conventional surgical and radio/chemotherapeutic treatments. A major asset of OVs lies in their multimechanistic mode of malignant cell killing, which differs from the cell death processes triggered by conventional anti-cancer agents This peculiarity can be rationalized by the virus need to prevent premature cytopathic effects (CPE) from interfering with virus production, and is therapeutically exploited to overcome the resistance developed by many tumor cells to conventional therapies. Oncolytic virotherapy can be considered from either virocentric or immunocentric points of view, depending on whether emphasis is placed on direct virus-induced oncolysis or on virus-mediated stimulation of anti-tumor immune responses In animal models, both mechanisms appear to act in combination, while having different relative weights depending on the individual target tumor. The above observations illustrative of parvovirus H-1 oncoselectivity have been further extended to animal models, in which H-1PV was reported to efficiently suppress tumor formation and to cause striking regression of established tumors (oncosuppression, see below) (Rommelaere and Cornelis, 1991)
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