Abstract 3487: Distant delivery of glioma-restricted oncolytic adenovirus loaded into a neural stem cell-based carrier prolongs the survival of animals with human glioblastoma

Abstract

Abstract Despite recent advancements in the treatment of brain tumors, the prognosis for patients with malignant glioblastoma (GBM) still remains poor due to the invasive nature of these tumors. In this context, our lab and others have investigated the unique inherent tumor tropic properties of neural stem cells (NSCs) as a novel platform for the targeted delivery of oncolytic adenovirus for anti-glioma therapy. NSCs hold great promise for glioma therapy because of their inherent ability to target satellite tumor foci throughout the brain. In this study, we report that the infection/loading of NSCs with oncolytic adenovirus upregulate various chemoattractant receptors such as CXCR4 (10-fold, P=0.0054), VEGFR2 (5-fold, P=0.0143) and significantly enhances glioma specific migration of NSCs both in vitro and in vivo. In a human glioma xenograft animal model, virus loaded NSCs retain a majority of their tumor homing capacity with minimal effect on their viability, and are capable of delivering a therapeutic payload to tumor cells located far from the original implanted site. Moreover, NSC-based cell carriers significantly reduce the non-specific distribution of therapeutic virus in the animal brain. Finally, distance delivery of NSCs-loaded with CRAd-S-pk7, a glioma restricted oncolytic adenovirus, in multiple orthotropic xenograft models of human glioma have shown the ability to inhibit tumor growth and increase median survival by about 38 days (54%) as compared to the animal group treated with the CRAd-S-pk7 alone (P=0.0416). Our data suggest that NSC-based cell carriers have the potential to improve the therapeutic efficacy of anti-glioma virotherapy by not only protecting the therapeutic virus from the host immune system, but also by enhancing targeted delivery of therapeutic virus at disseminated tumor sites. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3487. doi:1538-7445.AM2012-3487