A National Cancer Institute-designated Comprehensive Cancer Center

Make an appointment: 800-826-HOPE
Aboody, Karen S., M.D. Bookmark and Share

Laboratory of Karen S. Aboody, M.D.

Laboratory
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.
 
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.
 
For more information about Dr. Aboody, click here.
 

Karen S. Aboody, M.D. 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
 

Aboody, Karen S., M.D.

Laboratory of Karen S. Aboody, M.D.

Laboratory
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.
 
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.
 
For more information about Dr. Aboody, click here.
 

Lab Members

Karen S. Aboody, M.D. 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
  • Preparing a Thanksgiving meal is a huge responsibility, not just in terms of taste and presentation, but also in terms of food safety. Special care must be taken when handling, assembling and cooking the feast  – and this is never more true than when your guests will include immunosuppressed patients, such as c...
  • Celebrating the holidays with family and friends can be festive, but most of us definitely overeat. The average Thanksgiving meal is close to 3,000 calories – well above the average daily recommendation of 2,000 calories. Here, we serve up some tips from City of Hope dietitians Dhvani Bhatt and Denise Ackerman ...
  • A healthier Thanksgiving doesn’t have to mean a big plate of raw carrots and kale – not that there’s anything wrong with that. Instead, it can amount to a small change here, a small change there, and maybe a tweak beyond that. Dietitians at City of Hope, which promotes a healthful lifestyle as a way...
  • Joselyn Miller received a lifesaving bone marrow transplant at City of Hope two years ago. Here, she reflects on her gratitude as a bone marrow recipient and on giving back. By Joselyn Miller thank•ful adjective  \ˈthaŋk-fəl\ :  conscious of benefit received :  glad that something has happened or not happened, ...
  • When it comes to cancer, your family history may provide more questions than answers: How do my genes increase my risk for cancer? No one in my family has had cancer; does that mean I won’t get cancer? What cancers are common in certain populations and ethnicities? City of Hope experts have some guidance. “Your...
  • The body’s immune system is usually adept at attacking outside invaders such as bacteria and viruses. But because cancer originates from the body’s own cells, the immune system can fail to see it as foreign. As a result, the body’s most powerful ally can remain largely idle against cancer as the disease progres...
  • On Jan. 1, 2015, five City of Hope patients who have journeyed through cancer will welcome the new year with their loved ones atop City of Hope’s Tournament of Roses Parade float. The theme of the float is “Made Possible by HOPE.” The theme of the parade is “Inspiring Stories.” Her...
  • Are you thinking about switching from traditional cigarettes to e-cigarettes for the Great American Smokeout? Are you thinking that might be a better option than the traditional quit-smoking route? Think again. For lung expert Brian Tiep, M.D., the dislike and distrust he feels for e-cigs comes down to this: Th...
  • Hematologist Robert Chen, M.D., is boosting scientific discovery at City of Hope and, by extension, across the nation. Just ask the National Cancer Institute. The institution recently awarded Chen the much-sought-after Clinical Investigator Team Leadership Award for boosting scientific discovery at City of Hope...
  • Great strides have been made in treating cancer – including lung cancer – but by the time people show symptoms of the disease, the cancer has usually advanced. That’s because, at early stages, lung cancer has no symptoms. Only recently has lung cancer screening become an option. (Read more about the risks...
  • Identifying cures for currently incurable diseases and providing patients with safe, fast and potentially lifesaving treatments is the focus of City of Hope’s new Alpha Clinic for Cell Therapy and Innovation (ACT-I). The clinic is funded by an $8 million, five-year grant from the California Institute for Regene...
  • Cancer is a couple’s disease. It affects not just the person diagnosed, but his or her partner as well. It also affects the ability of both people to communicate effectively. The Couples Coping with Cancer Together program at City of Hope teaches couples how to communicate and solve problems as a unit. He...
  • Chemotherapy drugs work by either killing cancer cells or by stopping them from multiplying, that is, dividing. Some of the more powerful drugs used to treat cancer do their job by interfering with the cancer cells’ DNA and RNA growth, preventing them from copying themselves and dividing. Such drugs, however, l...
  • During October, everything seems to turn pink – clothing, the NFL logo, tape dispensers, boxing gloves, blenders, soup cans, you name it – in order to raise awareness for what many believe is the most dangerous cancer that affects women: breast cancer. But, in addition to thinking pink, women should...
  • In February 2003, when she was only 16 months old, Maya Gallardo was diagnosed with acute myelogenous leukemia (AML) and, to make matters much worse, pneumonia. The pneumonia complicated what was already destined to be grueling treatment regimen. To assess the extent of her illness, Maya had to endure a spinal ...