Abstract C125: Development of attenuated orf virus as a new generation oncolytic viral vector

Abstract

Abstract The orf virus (ORFV) possesses remarkable qualities that make it a potential viral vector for cancer therapy. Recently, the cancer-killing properties of ORFV have been demonstrated in a variety of human cancers, including nasopharyngeal carcinoma (NPC). Initially, we found that the ORFV-bearing wild-type genome was successful in eliminating two NPC cell lines derived from patients in Hong Kong and Taiwan, HK-1 and TW02, respectively. To make viral vectors safer for medical use, the oncolytic effects of two live attenuated ORFVs, which were created by removing one of the virulent factors, VEGF or CBP, were further evaluated in these two cell lines. Despite this attenuation, the two recombinant ORFVs were still able to effectively infect and kill NPC cells, particularly HK-1 cells. ORFV infection caused pyroptosis in NPC cells through GSDME cleavage, resulting in significant cell detachment and reduction in FAK and AKT activation during the early stages of infection. The innate immune response is also affected by ORFV infection, as shown by the increased chemotaxis of NK cells and synergistic effect of NK on the cytotoxicity of NPC cells caused by ORFV infection. Infection with both wild-type and CBP-deleted ORFVs significantly reduced HK-1 tumor growth in a xenograft mouse model, suggesting its potential as a therapeutic agent for NPC treatment. To maximize its therapeutic use, it is essential to comprehensively understand the mechanisms that drive the oncolytic activity of ORFV. Citation Format: Yumiko Yamada, Wei-Li Hsu, Yu-Chih Wang, Hao-Ping Liu. Development of attenuated orf virus as a new generation oncolytic viral vector [abstract]. In: Proceedings of the AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics; 2023 Oct 11-15; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2023;22(12 Suppl):Abstract nr C125.