Systematic Characterization of the Biodistribution of the Oncolytic Virus M1.

ABSTRACT

Oncolytic viruses are emerging as important tools for immunotherapy for cancer treatment; however, most of the clinically tested oncolytic candidates are still administered by intratumoral injection, and new viruses capable of intravenous injection are urgently needed. The M1 virus is a positive-sense single-stranded RNA virus that belongs to the alphavirus family, and it was identified as an oncolytic virus that can selectively replicate in and kill tumor cells after intravenous injection. To further develop M1 for clinical research through intravenous injection, we systematically investigated the biodistribution characteristics of the M1 virus in normal rats, cynomolgus monkeys, and tumor-bearing immunocompromised mice. The data showed that the M1 virus was eliminated gradually from normal tissue but replicated and increased rapidly in tumor tissue. More importantly, the virus also infiltrated the blood-brain barrier and specifically replicated in and killed malignant glioma in immunocompetent mice. Our data proved the tumor selectivity and safety of the M1 virus, supporting its further clinical development.