Stem Cells as Delivery Vehicles for Oncolytic Adenoviral Virotherapy

Justin      Kranzler; Matthew   A.   Tyler; Adam   M.   Sonabend; Ilya   V.   Ulasov; Maciej   S.   Lesniak

Abstract

Glioblastoma multiforme is the most common primary intracranial tumor in humans. Despite continued advances in cancer therapy, the outcome for patients diagnosed with this disease remains bleak. Novel treatments involving the use of conditionally replicating adenoviruses (CRAds) to target malignant brain tumors have undergone extensive research and proven to be a promising mode of glioblastoma therapy. CRAds are genetically manipulated to replicate within tumor cells, exhibiting a high degree of infectivity, cytotoxicity, and transgene expression. While the use of various CRAds has been deemed safe for intracranial injection in preclinical trials, a significant therapeutic effect has yet to be seen in patients. This shortcoming stems from the distribution limitations involved with local delivery of virolytic agents. To enhance this modality of treatment, stem cells have been explored as cellular vehicles in virotherapy applications, given that they possess an intrinsic tropism for malignant brain tumors. Stem cell loaded CRAd delivery offers a more specific and effective method of targeting disseminated tumor cells and forms the basis for this review.

Keywords: Stem cells, mesenchymal stem cells, neural stem cells, virotherapy, adenovirus, glioma, glioblastoma, brain cancer