1072. Delivery of Oncolytic Herpes Simplex Virus to Infiltrative Brain Tumor Sites Via Neuronal Stem Cells

Abstract

Top of pageAbstract Primary brain tumors, or Glioblastomas (GBMs), are devastating to each patient diagnosed due to the inability of current therapy to prolong survival. Thus, GBMs are prime candidates for trials of novel therapeutic modalities. One such novel therapy is oncolytic herpes simplex viruses (OHV). Oncolytic viral therapy (OV) has been explored as a potential therapy for many tumor types for many years. However, significant gains in ability to treat GBMs with OVs have not occurred. A significant problem with OV for GBM therapy is the inability of the virus to overcome the migratory infiltrative nature of tumor growth, a unique problem with GBMs. Thus, we determined the ability of neural stem cells (NSCs) to deliver OHV to sites of infiltrative tumor growth following intratumoral delivery of the stem cells. For this end, we utilized an infiltrative, HSV-sensitive GBM tumor model in syngenic, immunocompetent C57/Bl6 mice. We see greater distribution of the virus through the main injected tumor mass following NSC delivery than compared with that seen following OHV alone delivery. Furthermore, NSCs and virally infected cells are found in distal infiltrative tumor sites following NSC/OHV delivery. Delivery of the OHV via NSCs also leads to an alteration in the activation of the immune response to both viral and tumor antigens. Thus, delivery of infectious virus through the use of neural stem cells may be a feasible way to gain greater distribution of therapeutic agents such as OHV.