Year 5/NCE

High-grade gliomas, the most common primary brain tumors in adults, have a poor prognosis and remain incurable with current therapies. These devastating tumors present significant treatment challenges; 1) surgery may cause permanent neurologic damage; 2) surgery cannot remove the cancer cells that have invaded beyond the main tumor site; 3) most chemotherapy drugs cannot enter the brain because of the blood-brain barrier; and 4) chemotherapy drugs are toxic to normal tissues as well as tumor, causing undesirable side effects. Therefore, if therapeutic agents could be concentrated and localized to the tumor sites, treatment efficacy may improve while side effects are minimized.

Our goal is to bring to the clinic a human Neural Stem Cell (NSC)-based treatment strategy that produces potent localized anti-tumor effects while minimizing toxic side effects. NSCs have a natural ability to home to invasive brain tumor cells throughout the brain. NSCs, used as a delivery vehicle, offer a novel way to selectively target chemotherapy to brain tumor sites. NSCs are modified to express a certain enzyme (carboxylesterase; CE), that converts systemically administered prodrug (irinotecan) to a much more potent form (SN-38), that is up to 1000 times more effective at killing brain tumor cells.

Milestones reached in our fifth (final) year include:
(1) completion of safety/tox and efficacy study data analysis reports
(2) completion of clinical protocol
(3) completion of clinical lot for initiation of patient trial
(4) Regulatory documents including IBC, IRB, SCRO, NIH-RAC Protocol #13071241 all approved
(5) submission of final IND package to the FDA
(6) phase I trial initiation pending

Our results to date support our hypothesis that a safe and effective NSC-mediated therapy can be developed for clinical use in patients with high-grade glioma, with potential application brain tumor metastases, as well as metastatic cancers.