Neural Stem Cell-Mediated Treatment for Medulloblastoma

Background:

Medulloblastomas are the most common malignant childhood brain tumors. These tumors develop in the cerebellum, which is located in the lower part of the brain and is important in motor control. Despite recent advances in treatment, current therapies for medulloblastoma are often severely damaging to brain development and skeletal growth. Therefore, new treatments are critically needed to improve the survival and quality of life of children with medulloblastoma. Major obstacles to successful treatment of pediatric brain tumors include the blood-brain-barrier (BBB), which prevents many anti-cancer agents from entering the central nervous system. Neural stem cells (NSCs) offer a novel way to overcome these obstacles because they can cross the BBB, migrate to and selectively target tumor cells throughout the brain. NSCs can be genetically modified to act as delivery vehicles for targeted anti-cancer therapy, thereby increasing the tumor-localized concentrations of a drug while minimizing toxicity to normal tissues.

Project Goal:

The goal of this study is to determine the preclinical effectiveness of an NSC-mediated therapy against two subtypes of medulloblastoma.

We also found that NSCs do not migrate to non-cancerous brain areas or to peripheral tissues, suggesting that this approach would have minimal harm to surrounding tissue. We will next assess effectiveness of multiple NSC doses and schedules of the anti-tumor drug CPT-11 to optimize tumor targeting. Clinical translation of NSC-based delivery of chemotherapy could improve survival and minimize the serious brain damage caused by current radiation and chemotherapy regimens, thus improving the quality of survivorship of children with brain tumors.