A National Cancer Institute-designated Comprehensive Cancer Center

Make an appointment: 800-826-HOPE

Aboody, Karen S., M.D.

Laboratory of Karen S. Aboody, M.D.
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.
 
For more information about Dr. Aboody, click here.
 

Research

Neural Stem Cells Target Human Primary and Metastatic Tumors in Animal Models: Therapeutic Strategies
 
Introduction and Preliminary Data
Neural Stem Cells (NSCs), by virtue of their inherent migratory and tumor-tropic properties, represent a unique and potentially powerful approach for the treatment of invasive tumors. Utilized as a delivery vehicle to target and disseminate therapeutic gene products to tumor sites, NSCs may meet two major challenges facing current gene therapy strategies: effective delivery and distribution of a therapeutic agent throughout the tumor masses and to aggressive infiltrative tumor cells.  We previously demonstrated that murine C17.CD2 NSCs could deliver a bioactive therapeutically relevant molecule to effect a significant anti-tumor response in experimental intracranial glioma models. Further studies demonstrated retention of tumor-tropic properties when these NSCs were injected into the peripheral vasculature, even when the tumor was established outside the cranial vault, i.e. subcutaneous flank. When injected into the tail vein of animals with intracranial and/or subcutaneous flank tumors, the murine NSCs localized to both tumor sites, with little accumulation in normal tissues.
 
We previously demonstrated that murine C17.CD2 NSCs could deliver a bioactive therapeutically relevant molecule to effect a significant anti-tumor response in experimental intracranial glioma models. Further studies demonstrated retention of tumor-tropic properties when these NSCs were injected into the peripheral vasculature, even when the tumor was established outside the cranial vault, i.e. subcutaneous flank. When injected into the tail vein of animals with intracranial and/or subcutaneous flank tumors, the murine NSCs localized to both tumor sites, with little accumulation in normal tissues.
 
Neural Stem Cells Distribute Efficiently throughout Primary Brain Tumor Mass
CNS-1.GFP invasive rodent glioma cells, were implanted into the frontal lobe of adult nude mice followed 6 days later by transplantation of NSCs directly into the main tumor bed. Note efficient distribution of NSCs throughout main tumor bed, and localizing to invasive tumor islands and cells, and not seen elsewhere in the brain.
 
Neural Stem Cells Selectively Track Infiltrating Tumor Cells
Of note, whether NSCs are injected directly into tumor bed, or at a distance form main tumor (including ventricular or intravascular administration), they are able to localize to main tumor sites, invading tumor islands, and individual tumor cells in the brain.
 
Therapeutic Proof of Concept
The NSCs in the above figures were expressing a reporter gene. These NSCs can also be engineered to stably express therapeutic genes. We can therefore utilize them as cellular delivery vehicles to target therapeutic agents directly to tumor sites. In the following proof-of-concept paradigm, we achieve production of localized chemotherapy to produce a significant therapeutic effect in a metastatic brain tumor model. NSCs are engineered to produce an enzyme, cytosine deaminase, which can convert a systemically administered pro-drug (5-FC) to an active chemotherapeutic agent (5-FU), which diffuses out of the stem cells to selectively kill the surrounding dividing tumor cells. in vivo example shown in Figure 3, schematic representation of paradigm shown below:
 
NSCs expressing cytosine deaminase were injected into brain parenchyma of animals with established melanoma metastasis. After 3 days, in which time NSCs localized specifically to tumor sites, animals received tail vein injections of 5-FC prodrug for eight days. Representative brain tissue sections of untreated vs. treated animals shown. Tumor area is dark purple delineated by red outline.
 
Therapeutic Paradigm Schematic
In this case, stem cells were engineered to express the pro-drug activating enzyme, cytosine deaminase. Once cells are injected into animal tumor models, and localize to tumor sites, the 5-FC pro-drug is given systemically. Result is production of chemotherapeutic agent localized to tumor sites.
 

Lab Members

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
 
Our Scientists

Our research laboratories are led by the best and brightest minds in scientific research.
 

Beckman Research Institute of City of Hope is internationally  recognized for its innovative biomedical research.
City of Hope is one of only 41 Comprehensive Cancer Centers in the country, the highest designation awarded by the National Cancer Institute to institutions that lead the way in cancer research, treatment, prevention and professional education.
Learn more about City of Hope's institutional distinctions, breakthrough innovations and collaborations.
Develop new therapies, diagnostics and preventions in the fight against cancer and other life-threatening diseases.
 
Support Our Research
By giving to City of Hope, you support breakthrough discoveries in laboratory research that translate into lifesaving treatments for patients with cancer and other serious diseases.
 
 
 
 
NEWS & UPDATES
  • A common surgical device, often used for minimally invasive hysterectomies, may be riskier than previously thought because of its potential to spread several types of cancer, not just uterine cancer, a new study has found. One out of every 368 women treated with a power morcellator – a device that cuts the uter...
  • Skin cancer rates have been on the rise for years. On Tuesday, the U.S. surgeon general said: Enough. In issuing the first-ever Call to Action to Prevent Skin Cancer, acting Surgeon General Boris Lushniak described skin cancer as a “major public health problem” that requires action by all segments o...
  • Learn more about becoming a patient or getting a second opinion at City of Hope by visiting us online or by calling 800-826-HOPE (4673). City of Hope staff will explain what’s required for a consult at City of Hope and help you determine, before you come in, whether or not your insurance will pay for the ...
  • Counter-intuitive though it might seem, a prostate cancer diagnosis shouldn’t always lead to immediate prostate cancer treatment. Although prostate cancer is the second-leading cancer killer of men, behind lung cancer, and causes more than 29,000 deaths in the U.S. each year, in many cases, the tumors are...
  • Radiology is one of the cornerstones of any hospital. It is a key diagnostic branch of medicine essential for the initial diagnosis of many diseases and has an important role in monitoring a patient’s treatment and predicting outcome. Radiology is the specialty considered to be both the “eyes” and “ears” of med...
  • Donating blood and platelets saves lives. We all know this. Yet every summer, potential blood donors become distracted by vacations and schedule changes. As a result, blood donations fall dramatically across the nation, leaving hospitals frantically trying to bring in much-needed blood for their patients. Earli...
  • To be a great cancer hospital, you need a great oncology program. Just ask City of Hope – and Becker’s Hospital Review. The health care publishing industry stalwart, described as the “leading hospital magazine for hospital business news and analysis for hospital and health system executives,” recently selected ...
  • Diagnostic errors are far from uncommon. In fact, a recent study found that they affect about 12 million people, or 1 in 20 patients,  in the U.S. each year. With cancer, those errors in diagnosis can have a profound impact. A missed or delayed diagnosis can make the disease that much harder to treat, as the Ag...
  • Eleven years ago, lymphoma patient Christine Pechera began the long road toward a cancer-free life. She had been diagnosed with non-Hodgkin lymphoma and told by doctors elsewhere that her lifespan likely would be measured in months, not years. Refusing to give up, she came to City of Hope for a second opinion. ...
  • Brain surgery is not for the faint of heart. It takes courage, as well as curiosity and compassion. The truly great surgeons also have a desire to find new, and better ways, of healing the brain. Enter Behnam Badie, M.D., chief of neurosurgery at City of Hope. Now a pioneer in brain tumor treatment, Badie enter...
  • Elizabeth Budde, M.D., Ph.D., wants to encourage infighting. She aims to turn the immune system on itself — to the benefit of patients with acute myeloid leukemia, or AML. AML arises when abnormal white blood cells grow out of control, amassing in the bone marrow and interfering with normal blood cell developme...
  • Six, to date; more soon. Outpatient bone marrow transplants, that is. Finding new ways to deliver quality care with the greatest benefit is a priority for a patient-centered institution like City of Hope. For example, not every bone marrow transplant patient needs to check into the hospital for treatment. In fa...
  • The best measure of success in the fight against cancer is in lives saved and families intact, in extra days made special simply because they exist. Yuman Fong, M.D., chair of the Department of Surgery at City of Hope, understands what precedes that special awareness. When cancer strikes, one minute a person ma...
  • In cancer, expertise matters. So do survival rates, patient safety, patient services and many other factors. City of Hope understands this, as does U.S.News & World Report. The magazine’s 2014-2015 list of best hospitals for cancer once again includes City of Hope, ranking the institution 12 out of 900 elig...
  • At 29, Kommah McDowell was a successful young professional engaged to be married to her best friend. She worked in the financial services sector and kick-boxed to keep in shape and to relax. Then came the diagnosis of triple-negative inflammatory breast cancer, a rare and very aggressive form of breast cancer. ...