Concise Review: Neural Stem Cell‐Mediated Targeted Cancer Therapies

• Published in: Stem cells translational medicine 2018-10, Vol.7 (10), p.740-747
• Main Authors: Mooney, Rachael, Hammad, Mohamed, Batalla‐Covello, Jennifer, Abdul Majid, Asma, Aboody, Karen S.
• Format: Article
• Language: English
• Subjects: Animals; Antimitotic agents; Antineoplastic agents; Antineoplastic Agents - chemistry; Antineoplastic Agents - therapeutic use; Apoptosis; Blood-brain barrier; Brain cancer; Brain research; Brain tumors; Breast cancer; Cancer; Cancer therapies; Cellular therapy; Chemotaxis; Chemotherapy; Clinical translation; Clinical trials; Cytokines; Enabling Technologies for Cell Based Clinical Translation; Enzymes; Gene delivery systems in vivo or in vitro; Gene therapy; Glioma; Health aspects; Humans; Hypoxia; Immune system; Immunotherapy; Invasiveness; Kinases; Melanoma; Metastases; Metastasis; Morbidity; Mortality; Nanoparticles; Nanoparticles - chemistry; Nanoparticles - therapeutic use; Neoplasms - drug therapy; Neoplasms - pathology; Neoplasms - therapy; Neural stem cells; Neural Stem Cells - chemistry; Neural Stem Cells - cytology; Neural Stem Cells - transplantation; Neuroblastoma; Oligonucleotides; Oncology, Experimental; Oncolysis; Oncolytic Virotherapy; Ovarian cancer; Phototherapy; Prodrugs - chemistry; Prodrugs - therapeutic use; Progenitor cells; Proteins; Radiation therapy; Side effects; Solid tumors; Stem cells; TNF-Related Apoptosis-Inducing Ligand - chemistry; TNF-Related Apoptosis-Inducing Ligand - therapeutic use; Translation; Translational s and Reviews; Transplantation; Tumors; Vascular endothelial growth factor; Viral persistence; Viruses
• ISSN: 2157-6564; 2157-6580; 2157-6580
• DOI: 10.1002/sctm.18-0003

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 Engineering neural stem cells (NSCs) to deliver targeted anticancer payloads. Tumor‐tropic NSCs can be engineered to deliver anticancer agents selectively to tumor foci. Approaches explored include enzyme/prodrug gene therapy; oncolytic virotherapy; therapeutic protein delivery (antibody delivery shown as example); sustained‐release or stimuli‐responsive nanoparticle delivery; and extracellular vesicle oligonucleotide delivery.