Designing and building oncolytic viruses

Maroun, Justin; Muñoz-Alía, Miguel; Ammayappan, Arun; Schulze, Autumn; Peng, Kah-Whye; Russell, Stephen

For high seroprevalence viruses, one approach to circumvent viral neutralization by preformed antibodies is to engineer or switch the viral coat proteins. Some OVs (e.g., adenovirus) offer a menu of different serotypes, providing a basis for serotype switching between successive doses of the therapy to avoid antibody neutralization, although this does greatly complicate the product development pathway since each serotype is considered to be a distinct pharmaceutical product [82] . For monotypic viruses such as measles, serotype switching is not an option, but antimeasles antibodies can be circumvented by substituting the surface glycoproteins of measles with those of a related but noncross-reactive morbillivirus such as canine distemper virus [83] . Alternatively, the immunodominant epitopes of the measles surface glycoproteins can be modified by mutating key surface residues to eliminate them, or by introducing glycosylation signals so they are shielded by N-linked glycans [84] . It is worth noting that all of these virus engineering strategies have the potential to alter viral receptor usage and hence tumor cell tropism which may limit their utility [83, 85] .