830 mLIGHT-armed oncolytic myxoma virus combined with selinexor and PD-1 blockade reduces pulmonary metastatic burden in an immunocompetent murine melanoma model
Year: 2026
Type: conference-abstract
Abstract: Background Cancer remains the second leading cause of death worldwide, with the majority of mortality resulting from metastatic disease. Despite advances in targeted therapies, treatments for late stage cancers remain insufficient, highlighting the need for novel therapeutic strategies capable of controlling disseminated tumors. Oncolytic viruses (OVs) represent a promising class of anti-cancer agents that selectively infect malignant cells while simultaneously stimulating robust antitumor immunity. Unlike conventional therapies, OVs can promote systemic immunity capable of generating immunological memory and targeting metastatic lesions at distant sites. Myxoma virus (MYXV) is an attractive OV due to its favorable safety profile. MYXV is naturally restricted to rabbits and is nonpathogenic in humans, but can still kill cancer cells of human origin ( figure 1). Furthermore, MYXV can be engineered to express immunostimulatory transgenes, like LIGHT, to further enhance antitumor immunity.Methods In this study, we evaluated the therapeutic efficacy of a murine LIGHT (mLIGHT)-armed MYXV in combination with the chemotherapeutic selinexor and anti-PD-1 immune checkpoint blockade in a murine model of lung-metastatic melanoma. Experimental pulmonary metastases were established by intravenous injection of B16-F10 melanoma cells expressing firefly-luciferase (B16-F10-FLuc) into immunocompetent C57BL/6 mice (n = 10 per group). Mice received intranasal administration of mLIGHT-armed MYXV (5×10 7 FFU/mouse) two days post-tumor inoculation and every other day afterwards for five total treatments. Selinexor was administered orally, and anti-PD-1 was delivered intraperitoneally, each at 10 mg/kg dosages. Metastatic tumor burden was quantified by bioluminescence imaging of harvested lungs at the study’s endpoint.Results Mice treated with mLIGHT-armed MYXV in combination with either selinexor or anti-PD-1 exhibited significantly reduced pulmonary metastatic burden compared with PBS-treated controls. Treatment with mLIGHT-MYXV plus selinexor, mLIGHT-MYXV plus anti-PD-1, and the triple-combination regimen significantly reduced mean lung bioluminescent signal by 95.3%, 83.1%, and 95.7%, respectively, compared with PBS controls (one-way ANOVA, p < 0.0001). Notably, the triple-combination regimen produced the strongest antitumor effect, resulting in the greatest reduction in metastatic melanoma burden within the lungs. A subset of mice receiving either mLIGHT-MYXV plus selinexor or mLIGHT-MYXV plus anti-PD-1 exhibited no detectable pulmonary FLuc signal at study endpoint (2/10 mice per group). Notably, 5/10 mice receiving the triple-combination regimen lacked detectable pulmonary FLuc signal at study endpoint, compared with 0/10 PBS-treated controls ( figure 2).Conclusions Collectively, these findings demonstrate that arming MYXV with LIGHT and combining with selinexor and PD-1 blockade produces enhanced control of metastatic melanoma and supports the development of multimodal immunotherapeutic strategies for metastatic cancers.Ethics Approval All animal experiments were approved by the Institutional Animal Care and Use Committee (IACUC) of Arizona State University and conformed to all regulatory standards. The IACUC protocol number is 26-2171R.Abstract 830 Figure 1MYXV strictly infects and causes disease in rabbits, yet it can selectively replicate in cancer cells derived from non-host species like humans and mice, making it a strong candidate for cancer immunotherapyAbstract 830 Figure 2Combination therapy with mLIGHT-armed MYXV reduces pulmonary metastatic melanoma burden. Bioluminescent quantification of tumor burden in C57BL/6 mice (n = 10) with indicated treatments. Data are presented as mean + SEM. **p < 0.01, ***p < 0.001
Institution: Arizona State University
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,490
OpenAlex ID: W7225139054