Comparison of safety, delivery, and efficacy of two oncolytic herpes viruses (G207 and NV1020) for peritoneal cancer

Abstract

G207 and NV1020 are two replication -competent, multimutant oncolytic herpes simplex viruses evaluated in the current studies for their anticancer effects in the treatment of gastric cancer. Deletion of both 1 34.5 genes and inactivation of ICP6 ( ribonucleotide reductase ) allows G207 to selectively replicate within tumor cells. NV1020 is another attenuated recombinant herpes virus with deletions of the HSV joint region, with deletion of only one copy of the 1 34.5 gene, and with the ICP6 gene intact. In vitro, both G207 and NV1020 effectively infected, replicated, and killed human gastric cancer cells, with NV1020 being more effective at lower concentrations of virus. In a murine xenograft model of peritoneally disseminated gastric cancer, both NV1020 and G207 reduced tumor burden when given intraperitoneally ( i.p. ) at higher doses. When viral doses were lowered or when advanced tumor was treated, i.p. NV1020 was superior to i.p. G207. In vitro viral replication and cytotoxicity predicted the in vivo antitumor response. Intravenous delivery of either G207 or NV1020 failed to reduce tumor burden, demonstrating the importance of regional therapy as treatment for compartmentalized malignancy. Both agents were safe for use in animals, and immunohistochemistry performed on mouse tissue revealed selective viral targeting of tumor. Oncolytic therapy using genetically engineered HSVs represents a promising strategy for peritoneal malignancies.

Impact of novel oncolytic virus HF10 on cellular components of the tumor microenviroment in patients with recurrent breast cancer

“…A growing body of preclinical and clinical data suggests that oncolytic viral therapy could be an effective therapeutic modality in the treatment of advanced cancer. [5][6][7][8][9][10][11] Various strains of viruses, such as adenovirus, 12 herpes simplex virus, 13 Newcastle disease virus, measles virus, vesicular stomatitis virus and vaccinia virus 14 are being analyzed for their oncolytic capacity; some of these viruses have progressed to the clinical trial phase. Herpes simplex virus type 1 (HSV 1) is an ideal candidate for oncolytic viral therapy because of the following reasons: (a) it infects a broad range of hosts; (b) it causes lyses of the host cell at the end of viral replication; (c) it has a very large genome and therefore harbors many non-essential genes, mostly related to neuroinvasiveness that are expendable and can be replaced during the recombinant engineering process; (d) it can be controlled by antiviral drugs in the event of uncontrolled replication; and (e) its genome remains as an episome and does not incorporate in to the host genome, avoiding the risk of introducing mutations.…”

Widespread intratumoral virus distribution with fractionated injection enables local control of large human rhabdomyosarcoma xenografts by oncolytic herpes simplex viruses

“…For comparison with panel (b), fractionated dosing of UVinactivated virus on day 0 was also administered to tumors of similar size (c, UV-NV1066); for panel b vs. c, P ¼ .003. tion is thus difference in virus potency, since others have found G207 to be less potent than NV1020. 50 Importantly, Cinatl et al also demonstrated an antitumor effect following intravenous administration of virus that was potentiated by the addition of vincristine. Others have found a synergy between G207 and irradiation, at least in part due to the radiation-induced upregulation of cellular ribonucleotide reductase.…”

Oncolytic recombinant herpes simplex virus for treatment of orthotopic liver tumors in nude mice

“…Both rHSV 1716 and G207 were effective in animal models of malignant peritoneal disease induced by injection of human ovarian cancer cells (14,16). Intraperitoneal administration of G207 was also reported to have therapeutic potential against peritoneal tumors (17). rHSV R3616, an ICP34.5 deficient, replication-restricted HSV-1 was equally effective against chemotherapy-sensitive and -resistant ovarian cancer cells in vitro and in vivo (16).…”