[Antitumor immuno-virotherapy with attenuated strains of measles virus].

Abstract

Antitumor immuno-virotherapy involves the use of replicating oncolytic viruses capable of selectively infecting and killing tumor cells, with the aim of stimulating an antitumor immune response. Attenuated strains of measles virus (MeV) used as measles vaccines are good candidates. Attenuated MeVs use the CD46 molecule as a tumor cell entry receptor, but also CD150/SLAM and Nectin-4. The CD46 molecule blocks complement-mediated lysis and is frequently overexpressed by many cancer cell types, enabling the attenuated MeV to infect these cells. In addition, MeVs take advantage of defects in the antiviral type I interferon (IFN I) response in tumor cells to replicate, while this antiviral response blocks its replication in healthy cells. Attenuated MeVs display oncolytic properties against numerous cancers in vitro and in mouse models. They induce immunogenic cell death with infiltration of tumors by immune cells, notably T lymphocytes, thus activating the anti-tumor immune response. Several phase I and II clinical trials using different MeVs have been carried out, with encouraging results. Here, we provide an update on this therapeutic approach.