Abstracts from the ASENT 18th Annual Meeting

摘要

Oncolytic viruses (OV) represent antitumor effects in the ways of direct tumor lysis and by stimulating host tumor immunity, but maximum therapeutic effect of OV requires proper delivery into the tumor beds. Stem and immune cells are promising cellular vehicles for this OV delivery. However, there is a problem to this strategy: the OV will replicate and lyse within the carrier cell, meaning that the carrier cell has to be delivered to the host and reach the tumor to disperse the OV. We have engineered a double- vector system, where a replication-defective adenovirus can be switched to become oncolytic in the presence of Flp recombinase expressed by a replication-defective amplicon under tight transcriptional control of tumor hypoxia-regulatable elements. Human mesenchymal stem cells, infected with both vectors, remain viable for prolonged periods of time and do not generate OV under normoxic conditions, but placed under hypoxic conditions they will lyse and generate OVs.