Lister Vaccine Strain of Vaccinia Virus Armed with the Endostatin–Angiostatin Fusion Gene: An Oncolytic Virus Superior todl1520 (ONYX-015) for Human Head and Neck Cancer

Abstract

Oncolytic viral therapy represents a promising strategy for the treatment of head and neck squamous cell carcinoma (HNSCC), with dl1520 (ONYX-015) the most widely used oncolytic adenovirus in clinical trials. This study aimed to determine the effectiveness of the Lister vaccine strain of vaccinia virus as well as a vaccinia virus armed with the endostatin-angiostatin fusion gene (VVhEA) as a novel therapy for HNSCC and to compare them with dl1520. The potency and replication of the Lister strain and VVhEA and the expression and function of the fusion protein were determined in human HNSCC cells in vitro and in vivo. Finally, the efficacy of VVhEA was compared with dl1520 in vivo in a human HNSCC model. The Lister vaccine strain of vaccinia virus was more effective than the adenovirus against all HNSCC cell lines tested in vitro. Although the potency of VVhEA was attenuated in vitro, the expression and function of the endostatin-angiostatin fusion protein was confirmed in HNSCC models both in vitro and in vivo. This novel vaccinia virus (VVhEA) demonstrated superior antitumor potency in vivo compared with both dl1520 and the control vaccinia virus. This study suggests that the Lister strain vaccinia virus armed with an endostatin-angiostatin fusion gene may be a potential therapeutic agent for HNSCC.

A Novel Therapeutic Regimen to Eradicate Established Solid Tumors with an Effective Induction of Tumor-Specific Immunity

“…1C). The level of viral replication for both viruses in the 3 cell lines are comparable with some human cancer cell lines, although they are still lower than those in the majority of human cancer cell lines that we previously screened (31,32). After intratumoral administration of adenovirus and vaccinia virus into the established tumor model of HPD-1NR in vivo, proteins of both viruses were expressed in tumor cells (Fig.…”

Vaccinia Virus Outperforms a Panel of Other Poxviruses as a Potent Oncolytic Agent for the Control of Head and Neck Squamous Cell Carcinoma Cell Lines

“…Of the poxvirus family of viruses, only VACV has been characterized for oncolytic activity in HNSCC [7,8]. To begin comparisons of the oncolytic abilities of different poxviruses, we first determined the ability of four different poxviruses (MYXV, VACV, RCNV and TANV) to infect six well-characterized HNSCC lines.…”

“…MYXV, RCNV and TANV have all demonstrated oncolytic activity in various preclinical models [4,11,12] and do not cause infection in normal human tissue with the exception of tanapox virus which can produce a localized, limited infection [12]. Although numerous investigators have studied a variety of oncolytic viruses including various strains of vaccinia virus [7,15,16], this is the first evaluation of a panel of poxviruses for the control of head and neck cancer.…”

“…Clinical trials, testing a range of viruses, including adenovirus, reovirus and herpesvirus, to control HNSCC are underway [2]. However, outside of tests with vaccinia virus, the poxvirus family of viruses has not been characterized for oncolytic activity in HNSCC [7,8]. …”

Viral gene therapy for head and neck cancer

“…19 A vaccinia virus vector armed with an endostatin-angiostatin fusion gene demonstrated superior anti-tumour efficacy for head and neck cancer in a pre-clinical study. 20 Apoptosis is a tightly regulated process of programmed cell death. It can be induced in cancer cells therapeutically through the manipulation of apoptosis-inducing ligands and pro-or anti-apoptotic molecules.…”