Overcoming the limitations of locally administered oncolytic virotherapy

Abstract

Adenovirus (Ad) has been most extensively evaluated gene transfer vector in clinical trials due to facile production inhigh viral titer, highly efficient transduction, and proven safety record. Similarly, an oncolytic Ad, which replicatesselectively in cancer cells through genetic modifications, is actively being evaluated in various phases of clinical trials asa promising next generation therapeutic against cancer. Most of these trials with oncolytic Ads to date have employedintratumoral injection as the standard administration route. Although these locally administered oncolytic Ads haveshown promising outcomes, the therapeutic efficacy is not yet optimal due to poor intratumoral virion retention,nonspecific shedding of virion to normal organs, variable infection efficacy due to heterogeneity of tumor cells,adverse antiviral immune response, and short biological activity of oncolytic viruses in situ. These inherent problemsassociated with locally administered Ad also holds true for other oncolytic viral vectors. Thus, this review will aim todiscuss various nanomaterial-based delivery strategies to improve the intratumoral administration efficacy of oncolyticAd as well as other types of oncolytic viruses.