The Identification and Development of a Novel Oncolytic Virus: Alphavirus M1.

Abstract

Oncolytic virotherapy represents an ideal therapeutic platform for cancer in which natural or engineered viruses selectively replicate in and destroy tumor cells, whereas sparing normal cells. Oncolytic virotherapy is considered as a key contributor in modern immunotherapy. However, several challenges remain with regard to exploiting the potential of oncolytic viruses, such as the lack of biomarkers for precise treatment, the difficulty of systemic administration because of pre-existing neutralizing antibodies to popular oncolytic viral vectors in human serum and the lack of mature lyophilization technology for convenient transport and preservation of viral preparations. The M1 strain, which was isolated on Hainan Island of China in the 1960s, is a member of the alphavirus genus Togaviridae family. It was identified as a novel oncolytic virus in 2014. During the development of M1 virus, many challenges have been overcome: several biomarkers have been identified for precise treatment; systematic administration of M1 is suitable and feasible because of the extremely low percentage of pre-existing neutralizing antibodies in the general population, and a lyophilized powder that maintains high biological stability has been developed. This review provides an encyclopedia of studies supporting M1 as an oncolytic virus, including the biological characteristics, tumor selectivity and its mechanism, tumor killing mechanism, combination therapy, and nonclinical pharmacokinetics of M1 virus. The future development direction of oncolytic virus M1 is also discussed at the end of the review.