Natural oncolytic activity of live-attenuated measles virus against human lung and colorectal adenocarcinomas
Nicolas Boisgerault, Jean-Baptiste Guillerme, Daniel Pouliquen, Mariana Mesel-Lemoine, Carole Achard, Chantal Combredet, Jean-François Fonteneau, Frédéric Tangy and Marc Grégoire
Lung and colorectal cancers are responsible for approximately 2 millions deaths each year worldwide. Despite continual improvements, clinical management of these diseases remains challenging and development of novel therapies with increased efficacy is critical to address these major public health issues. Oncolytic viruses have shown promising results against cancers that are resistant to conventional anti-cancer therapies. Vaccine strains of measles virus (MV) exhibit such natural anti-tumor properties by preferentially targeting cancer cells. We tested the ability of live-attenuated Schwarz strain of MV to specifically infect tumor cells derived from human lung and colorectal adenocarcinomas, and demonstrated that live-attenuated MV exhibits oncolytic properties against these two aggressive neoplasms. We also showed that Schwarz MV was able to prevent uncontrollable growth of large, established lung and colorectal adenocarcinoma xenografts in nude mice. Moreover, MV oncolysis is associated with in vivo activation of caspase-3 in colorectal cancer model, as shown by immunohistochemical staining. Our results provide new arguments for the use of MV as an anti-tumor therapy against aggressive human malignancies.