Neural Stem Cells and Cancer Treatment

My translational research laboratory focuses on neural stem cells (NSCs) and their therapeutic clinical applications for invasive brain tumors and metastatic solid tumors. Our novel findings have demonstrated the inherent tumor-tropic properties of NSCs, and their use as delivery vehicles to selectively target therapeutic agents to invasive tumors, including primary and secondary brain tumors, neuroblastoma, and breast carcinoma. We and others have demonstrated their ability to track and localize to infiltrating tumor cells when delivered into the brain, and metastatic tumor sites when delivered intravenously - making NSCs an attractive gene therapy vehicle with tremendous clinical potential.

In 2010, we received FDA approval for a first-in-human clinical trial for NSC-mediated therapy for high-grade glioma patients. This phase I study is ongoing at COH, supported by NCI/NIH funding.  Selected members of my laboratory are HIPAA and GMP trained, and prepare the NSCs for patient transplantation. In 2010, we also received an $18MM California Institute of Regenerative Medicine (CIRM) Disease Team Award to develop a second-generation enzyme/prodrug stem cell-mediated cancer therapy. (PI: K Aboody, Co-PIs: J Portnow, L Couture). This milestone driven translational research project is planned to result in a new FDA IND submission for brain tumor treatment in 2014. The therapeutic paradigm uses NSCs to deliver a CPT-11 (irinotecan) activating enzyme to increase its tumor-killing effect up to 1000 fold at the tumor sites. We believe this NSC-mediated treatment may have applications for other cancers as well.

We use various preclinical tumor models to test intracranial and intravenous delivery of NSCs to target various therapeutic agents to tumor sites. Therapeutic approaches being explored include enzyme/prodrug, oncolytic virus, antibody, and small molecule drug delivery.  Our lab has many leading-edge, collaborate projects in progress, including an NIH/NINDS U-01 with Univ. of Chicago (PI: M Lesniak), that is planned to lead to a new NSC-mediated clinical trial in 2014.  We are also working closely with CHLA, USC (R Moats) on iron labeling of NSCs for MRI cellular tracking. We have currently completed toxicity studies, and have submitted an amendment to the FDA to add this iron-labeling of NSCs to our current clinical trial. This would be a first in human use of ferumoxytol (Feraheme) as a cell tracker in patients.  In collaboration with Drs. M Barish and C Glackin, we are also trying to 1) identify the biological mechanisms and signally pathways involved in the directed migration of NSCs to tumor cells; 2) investigate the endogenous stem cell response to tumors; and 3) investigate the origin and progression of brain and breast cancers. The field of stem cell research is at the frontier of medical research – there are many exciting directions of investigations to pursue in order to better understand their function and development, with a wide array of potential clinical applications to explore.

Lucy Ghoda Ph.D.
CIRM Disease Team Project Manager

Joseph Najbauer, Ph.D.
Associate Research Professor

Margarita Gutova, M.D.
Assistant Research Professor

Rachael Mooney, Ph.D.
Post-doctoral CIRM Scholar

Donghong Zhao, Ph.D.
Post-doctoral Fellow

Marianne Metz
Staff Scientist

Elizabeth Garcia, R.V.T.
Research Associate II

Soraya Aramburo
Research Associate II

Zhongqi Li, Ph.D.
Research Associate II

Kelsey Herrmann, B.S.
Research Associate II

Tien Vo
Research Associate I

Revathiswari Tirughana, B.S.
Research Associate I

Yelena Abramyants,
Laboratory Technician

Valerie Valenzuela,
Laboratory Technician

Monika Polewski, B.A.,
City of Hope Graduate Student

Patrick Perrigue, B.S
City of Hope Graduate Student

Megan Gilchrist
CIRM Bridges Intern

Michael Silva
CIRM Bridges Intern

Kenna Schnaar
CIRM Bridges Intern

Elizabeth Ochoa
Senior Secretary, Dr. Aboody’s Laboratory