Neural stem cells as therapeutic delivery vehicles for malignant brain tumors

Abstract

Malignant brain tumors are nearly untreatable due to their highly infiltrative nature and resistance to existing therapies. The main reason for recurrent tumor growth is believed to be the presence of tumor cells that migrate great distances into the brain tissue. In addition, poor delivery of therapeutics to the tumors due to blood-brain barrier limits the clinical success of currently available systemically delivered antitumor therapies. Recently, a different mode of therapeutic delivery, whereby therapeutic biomolecules are expressed by tumor-tropic neural stem cells (NSCs), has gained considerable attention. Exploiting the intrinsic tumor-homing ability of NSCs, the past decade has witnessed significant advances in the discovery and development of NSC-based therapies for malignant brain tumors. Prodrug converting enzymes, immunomodulatory cytokines, pro-apoptotic (tumouricidal) agents, growth-inhibiting factors, anti-angiogenic agents, and viral particles have been among the most commonly studied antitherapeutic molecules produced by NSCs. While the mechanisms of tumor-directed NSC migration and fate of NSCs after engrafting are still not truly understood, the results from current preclinical tumor models have demonstrated promising utility for NSCs as "armed vehicles" in treatment of aggressive brain tumors. Indeed, the first clinical trial with NSC-delivered antitumor agents is now in progress for recurrent gliomas.