Designing and building oncolytic viruses

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

In light of the inconvenience and undesirability of OV shedding, there is interest in engineering strategies that may selectively interfere with the process. As one example, wild-type measles virus is a highly transmissible airborne virus that uses the nectin-4 receptor to enter into airway epithelial cells from whence its progeny are shed into respiratory secretions [192, 193] . Eliminating the nectin-4 tropism by strategically mutating key surface residues in the hemagglutinin attachment protein results in a virus that still causes measles in nonhuman primates, but which is no longer shed into respiratory secretions or urine [194] . Measles virus RNA (but not infectious virus) was detected in the blood, urine and saliva of myeloma patients up to 3 weeks after IV administration of an oncolytic measles virus, especially at higher dose levels, and it is possible that this shedding might be eliminated by using a nectin-4 blind version of the virus [195] . Virus shedding has also been detected in human clinical trials of HSV, reovirus, vaccinia, reovirus and adenovirus oncolytics, but was less readily detected following IT therapy with oncolytic VSV and polioviruses [167] . However, future science group www.futuremedicine.com it should be noted that while genome sequences have been detected in shed material, infectious virus particles have not been recovered.