Aptamer-Fortified VV-GMCSF-Lact for Systemic Glial Tumor Virotherapy

Virotherapy represents a promising approach for cancer treatment. However, when administered intravenously, oncolytic viruses are often hampered by neutralization from antibodies, reducing their antitumor efficacy. Aptamers offer a potential solution by shielding viral particles from neutralizing antibodies and prevent viral particle aggregation. In this study, human glioblastoma xenografts were orthotopically implanted in immunocompromised ICR mice. The therapeutic agents (VV-GMCSF-Lact-Apt1, VV-GMCSF-Lact-Apt2 or VV-GMCSF-Lact) were administered intravenously. Using magnetic resonance imaging, we observed a decrease in tumor growth in all experimental groups. Using the Kaplan-Meier method, it was shown that the mouse survival in the VV-GMCSF-Lact-Apt1, VV-GMCSF-Lact-Apt2 groups was higher than in the control group. The level of key cytokines (IL-1, IL-10, TNF-alpha) in mouse plasma was measured using ELISA. A study of cytokine levels (IL-1, IL-10, and TNF-) showed that the aptamers shift the immune response from a pro-inflammatory systemic response, by reducing IL-1, to an anti-tumor one, with an increase in TNF-. In histological analysis, the most destructive changes in tumor tissue were observed in the VV-GMCSF-Lact-Apt2 group, while the morphology of organ tissues (spleen, liver, kidneys and lungs) did not differ between the control and experimental groups. Thus, our results demonstrate a synergistic antitumor effect of the aptamer in combination with the oncolytic virus against glioblastoma tumor xenografts.