oncolytic adenovirus ICVB-1042

A genetically-engineered, replication competent, optimized E2 transcription factor (E2F)-dependent oncolytic adenovirus (Ad) composed of an Ad serotype 5 (Ad5) backbone that contains genomic modifications to include an Ad5/Ad34 chimeric fiber and dual modifications in E1A and E4orf6/7, and a modified capsid hexon protein, with potential antineoplastic activity. Upon administration, the oncolytic adenovirus ICVB-1042 selectively targets and binds to CD46 that is overexpressed on many cancer cells. Upon viral entry, ICVB-1042 infects and specifically replicates in tumor cells, which may result in tumor cell lysis. ICVB-1042 replicates only in cells with defects in the p16/Rb/E2F pathway, attributed to a mutation common in many solid tumors, and protects normal, non-proliferative cells from viral-mediated toxicity. The Ad5/Ad34 mutation improves viral entry into target tumor cells, enhancing tropism by enabling and increasing viral entry via CD46. The modifications in E1A and E4orf6/7 increases tumor selectivity. The modified capsid hexon protein allows for IV delivery and mediates cell interaction with CD46. ICVB-1042 includes expression of a fluorescent reporter protein (YPet) to aid in tracking viral replication.