Maintaining and loading neural stem cells for delivery of oncolytic adenovirus to brain tumors

Abstract

Despite recent advancements in the treatment of cancer, the prognosis for patients with malignant brain tumors remains poor. The success of currently available therapies has been limited in part because of the disseminated nature of these tumors. Furthermore, most of these tumors, when in a high-grade form, are resistant to chemo- and radiotherapy. Taking the above considerations into account, effective treatment of these cancers not only requires the development of new means to target tumor burdens that have dispersed significantly from their site of origin, but also therapeutic approaches which can appropriately discriminate between tumor cell and normal brain. In the past two decades, novel approaches involving the use of oncolytic adenoviruses to target ­malignant brain tumors have undergone extensive investigation and proven to be an effective mode of antiglioma therapy. While the use of various oncolytic adenoviruses has been proven to be safe for local delivery in preclinical and clinical trials, the successful application of this approach in the clinic has been hampered by the host immune response against the viral vector. The discovery of the inherent tumor-tropic properties of neural stem cells (NSCs) provides a unique opportunity that employs NSCs as a cellular vehicle to track tumor cells and deliver therapeutic oncolytic virus. This presents a novel platform for targeted delivery of oncolytic adenovirus to disseminated tumors selectively while hiding the therapeutic virus from the host immune system. NSC loaded with an oncolytic adenovirus offer a more selective and effective method of targeting satellite tumor burdens and this chapter reviews the methodology associated with this unique approach.