Repeat Systemic Delivery of Cross-Neutralization Resistant Synthetic Vesiculoviruses Immunomodulates the Tumor Microenvironment.

The clinical efficacy of systemic oncolytic virotherapy (OV) is constrained by the rapid development of neutralizing antibodies (nAbs), which prevent repeat systemic administration, a critical barrier to sustained anti-tumor immunity. Vesiculoviruses offer potent oncolytic and immunogenic potential. However, leveraging their serological diversity for repeat dosing remains unexplored.