Concise Review: Neural Stem Cell-Mediated Targeted Cancer Therapies

Abstract

Cancer is one of the leading causes of morbidity and mortality worldwide, with 1,688,780 new cancer cases and 600,920 cancer deaths projected to occur in 2017 in the U.S. alone. Conventional cancer treatments including surgical, chemo‐, and radiation therapies can be effective, but are often limited by tumor invasion, off‐target toxicities, and acquired resistance. To improve clinical outcomes and decrease toxic side effects, more targeted, tumor‐specific therapies are being developed. Delivering anticancer payloads using tumor‐tropic cells can greatly increase therapeutic distribution to tumor sites, while sparing non‐tumor tissues therefore minimizing toxic side effects. Neural stem cells (NSCs) are tumor‐tropic cells that can pass through normal organs quickly, localize to invasive and metastatic tumor foci throughout the body, and cross the blood‐brain barrier to reach tumors in the brain. This review focuses on the potential use of NSCs as vehicles to deliver various anticancer payloads selectively to tumor sites. The use of NSCs in cancer treatment has been studied most extensively in the brain, but the findings are applicable to other metastatic solid tumors, which will be described in this review. Strategies include NSC‐mediated enzyme/prodrug gene therapy, oncolytic virotherapy, and delivery of antibodies, nanoparticles, and extracellular vesicles containing oligonucleotides. Preclinical discovery and translational studies, as well as early clinical trials, will be discussed. Stem Cells Translational Medicine 2018;7:740–747

Quantitative Evaluation of Intraventricular Delivery of Therapeutic Neural Stem Cells to Orthotopic Glioma

“…Specifically, the major advantages include: (1) the ability to dose escalate NSCs beyond volume restrictions for ICT administration; (2) improved NSC viability in CSF; (3) no intratumorally placed catheter tips; (4) improved feasibility of performing multi-center studies; and (5) potential for CE-NSC-mediated gene therapy for treating leptomeningeal metastases from primary and metastatic brain tumors. Beyond the current NSC-based enzyme/prodrug converting strategies to increase levels of cytotoxic chemotherapy in brain tumors, we envision using our tumor-tropic NSCs as a platform technology can be further modified for tumor-localized delivery of a variety of anti-tumor products, such as apoptotic agents, oncolytic viruses, and antibodies, which could potentially be administered serially or in combination to maximize therapeutic benefit (32). Therefore, the impact of optimizing the delivery of NSCs may be far-reaching.…”

A doxycycline-inducible C17.2 neural stem cell-based combination of differentiation and suicide gene therapy for an in vitro tumorigenic C6 glioma model

“…Multiple kinds of gene therapies have been developed to cure brain cancers, including suicide gene therapy, cytokine-mediated gene therapy, tumor suppressor gene therapy and oncolytic gene therapy [7][8][9][10]. Among them, suicide gene therapy is the most frequently used approach to cure glioma both in preclinical studies and in clinical trials [11]. The mechanism of this strategy involves converting a nontoxic prodrug into a cytotoxic agent by the specific suicide gene, which is usually not expressed or expressed at a low level in mammalian cells [7].…”

Human Olfactory Bulb Neural Stem Cells (Hu-OBNSCs) Can Be Loaded with Paclitaxel and Used to Inhibit Glioblastoma Cell Growth

“…Beside their potential application as an effective cellular therapy for central nervous system (CNS) degenerative and traumatic diseases, engineered neural stem cells (NSCs) might represent a new effective modality for cancer therapy [1].…”