Abstract 6796: PoxSTG, a novel chimeric poxvirus with improved oncolytic potency

Abstract

Abstract Oncolytic virus (OV) therapy has emerged as a promising approach for cancer treatment with the potential to be less toxic and more efficient than classic cancer therapies. Various types of OVs in clinical development, including Vaccinia virus (VACV)-derived OVs, have shown good safety profiles, but limited therapeutic efficacy as monotherapy in some cancer models. Many different methods have been employed to improve the oncolytic potency of OVs. We used a directed evolution process, pooling multiple species of orthopoxviruses to generate chimeric poxviruses with increased oncolytic properties. Through selective pressure by successive passages on human tumor cells, a new chimeric oncolytic poxvirus, named PoxSTG, was derived. The chimeric viral genome contains, in addition to sequences from several strains of Vaccinia virus, sequences of Rabbitpox virus and Cowpox virus. Compared with its parental viruses, PoxSTG has demonstrated superior oncolytic characteristics, and was notably attenuated in normal primary cells. PoxSTG has superior secretion of extracellular-enveloped virus (EEV) compared to all parental strains inducing higher dissemination of the virus into the tumors and more resistance to neutralization. PoxSTG was saved and showed potent antitumor effects in several syngeneic and xenograft mouse models of cancers. Furthermore, PoxSTG exerted low-dose antitumor effects in virus-injected and non-virus-injected distant tumors in a CRC xenograft model, demonstrating strong virus spread to distant tumors. All these data demonstrate the potential of PoxSTG as a novel therapeutic agent for cancer treatment. Citation Format: Philippe Erbs, Annie Findeli, Johann Foloppe, Juliette Kempf, Isabelle Farine, Baptiste Moreau, Julie Hortelano, Christelle Pichon, Jules Deforges, Eric Quemeneur. PoxSTG, a novel chimeric poxvirus with improved oncolytic potency. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6796.