Activity of a group B oncolytic adenovirus (ColoAd1) in whole human blood.
Di Y., Seymour L., Fisher K.
Intravenous (i.v.) delivery of therapeutic viruses to human patients exposes virus particles to the potentially neutralising environment of the human bloodstream, where many components of the innate and adaptive immune system provide a formidable barrier to virus infection of target cells. Here we assess the haemocompatibility of ColoAd1, an oncolytic adenovirus currently undergoing clinical assessment for treatment of disseminated cancer by i.v. delivery. Compared with the commonly used serotype Ad5, ColoAd1 (which has a capsid derived from Ad11p) showed only minor inhibition of oncolytic activity by pooled human serum or washed human blood cells, with the amount of ColoAd1 required to kill cancer cells in vitro (the IC50) increasing <10-fold. However, some virus-blood interactions are concentration- and context-dependent, requiring study in whole, undiluted, human blood. ColoAd1 showed <50-fold increases in the IC50 in whole blood from most donors, whereas the activity of Ad5 was ablated. Extrapolating these findings to the clinical situation indicates that ColoAd1 would 'breakthrough' neutralisation in some patients receiving as few as 10(10) ColoAd1 particles i.v., and in most patients receiving doses of 10(12) or above, well within the achievable dose range.