Concise Review: Neural Stem Cell-Mediated Targeted Cancer Therapies

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.