Tumor Targeting-Retargeted Adenovirus

Abstract

Adenovirus (Ad) has been applied for gene therapy in various applications. The current Ad vector system has two critical problems; low transduction of the target cancer cells and high transduction of nontarget normal organs. To address these issues, we have been working on “retargeting” of Ad vectors via transductional or transcriptional targeting. Transductional targeting has been achieved with application of various bridging moieties, genetical modification of vector capsid, or chemically coating viral particles. On the other hand, transcriptional targeting has been performed by employing natural or artificial transcriptional control elements with desired selectivity profile. In the field of cancer gene therapy, such retargeting has achieved augmented infectivity in the cancers that have been difficult to transduce with conventional Ad vector, as well as cancer specific transgene expression for avoiding toxicity. Success in cancer gene therapy requires vector design reflecting the pathological/physiological profile of the target disease, such as conditionally replicative adenovirus with combined retargeting mechanisms incorporated. In addition, we must continue to seek new targeting modalities because different tumor context always imposes unique challenges with respect to disease targeting. While reliable preclinical/clinical studies are necessary to establish a legitimate role of adenoviral retargeting in the field of cancer gene therapy, it is obvious that better vector targeting should leads to more potent and safe adenovirus based cancer therapeutics.