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.

Neural Stem Cell-Mediated Cancer Treatment

Overview: Neural stem cells (NSCs) have a natural ability to home to malignant tumors and invasive tumor cells, making them an ideal delivery vehicle for transporting therapeutic agents to tumor sites.  Dr. Aboody and colleagues at COH were the first in the world to move this therapeutic strategy from “bench to bedside” for brain tumor patients, demonstrating safety of their NSCs. 
 
My translational research laboratory focuses on neural stem cells (NSCs) and their therapeutic applications for primary and metastatic tumors. Our novel findings have demonstrated the inherent tumor-tropic property of NSCs, and their use as cellular delivery vehicles to effectively target and deliver therapeutic payloads to invasive tumor sites, including brain tumors and metastatic cancers. Their capacity for tracking infiltrating tumor cells and localizing to distant micro-tumor foci make NSCs a novel and attractive tumor selective delivery vehicle with tremendous clinical potential. In effect, the NSCs serve as a platform for tumor-localized therapy, which should also minimize toxicity to normal tissues. Our current research focuses on modifying human NSCs to deliver different therapeutic agents to tumor sites in animal models.
 
Clinical Trials: In 2013, we completed a first in-human FDA approved safety/feasibility NSC clinical trial at City of Hope in patients with recurrent high-grade gliomas (clinical PI: Dr. Jana Portnow, MD).  The NSCs delivered an enzyme (cytosine deaminase; CD) that converts an inactive prodrug (5-flurocytosine; 5-FC) to an active chemotherapeutic agent (5-Flurouracil; 5-FU).  The 5-FU produced by the NSCs diffuses into surrounding brain tumor tissue, selectively killing dividing tumor cells.  By producing the chemo drug only at the tumor sites, systemic side effects are minimized.  Results of this study demonstrated: 1) safety of administering therapeutic NSCs into the brain tumor resection cavity or biopsy site; 2) proof of concept for tumor-localized chemotherapy production – demonstrating that the CD-expressing NSCs were able to convert oral 5-FC to the active chemo drug 5-FU, locally in the brain; and 3) no significant immune response following one round of treatment.  A phase I dose escalation, multi-treatment round study is currently accruing patients at COH.
 
Active Research
1. NSCs delivering a prodrug activating enzyme for tumor-localized chemotherapy production:   CD-NSCs + 5-FC → 5-FU
Funding: STOP Cancer, COH, The Rosalinde and Arthur Gilbert Foundation, The Ziman  Family  Foundation, NIH-NCI (Portnow, Aboody)
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
NSCs are genetically modified to express cytosine deaminase (CD).  When the inactive prodrug 5-FC is administered, it crosses the BBB and gets converted to the active chemotherapeutic 5-FU by the CD expressing NSCs locally at the brain tumor sites.  In effect, allowing for tumor localized chemotherapy production, and reducing toxic side effects to normal tissues.
 

2. NSCs delivering a prodrug activating enzyme for tumor-localized chemotherapy production:   CE-NSCs + IRN → SN-38
Funding:  California Institute of Regenerative Medicine, NIH-U01, The Rosalinde and Arthur Gilbert Foundation, STOP Cancer, Mary Kay Foundation (Berlin, Aboody)
 
NSC-mediated CE/Irinotecan (CPT-11) enzyme/prodrug therapy.  NSCs localize to metastatic tumor sites and express the CE enzyme. CE converts the intravenously administered CPT-11 (irinotecan) prodrug to the active chemotherapeutic drug SN-38.  SN-38 is highly toxic to the surrounding tumor cells
 
In 2010, we were granted an $18M CIRM Disease Team Award to move a 2nd generation enzyme/prodrug therapeutic toward clinical trials (Co-PIs:  Jana Portnow, MD and Larry Couture, PhD). Collaborators include the Synold lab for pharmacology, the Barish lab for 3D tumor reconstruction, the Forman lab (C Brown) for xenogen imaging and tumor modeling, and the Moats lab at Children’s Hospital Los Angeles for MRI imaging. We also work closely with the Center for Biomedicine & Genetics and the Office of IND Development and Regulatory Affairs. An IND has been submitted and we expect to initiate a phase I study for this NSC-mediated brain tumor therapy in 2015.  We are also funded $4.7M by an NIH-U01 (in collaboration with CHLA and St. Jude) to move this same product to clinical trial for pediatric patients with metastatic neuroblastoma by 2017.
 

3. NSCs delivering internalized gold nanoparticles for thermal ablative therapy
in collaboration with Jacob Berlin laboratory, COH
 
After loading NSCs with gold nanorods (NSC-AuNPs), they are administered (current preclinical investigations focusing on bladder and prostate cancer).  Following migration of NSCs to tumor  sites, localizing the gold particles, near infrared laser is applied, causing the gold nanoparticles to  vibrate and generate heat – ‘burning’ surrounding tumor tissue.
Funding:  COH, The Rosalinde and Arthur Gilbert Foundation, STOP Cancer, Alvarez Family  Charitable Foundation, Mary Kay Foundation (Berlin, Aboody), Ladies Auxiliary Veteran’s Grant (Mooney)
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
4. NSCs delivering external nanoparticles for small molecule drug delivery
in collaboration with Jacob Berlin laboratory, COH
   
In collaboration with Dr. Berlin we are constructing NSC-NP hybrids, where the NPs are being  constructed to release drug after NSCs reach the tumor.  The NPs will be externally bound to the  NSCs.  Our initial preclinical studies are focused on peritoneal ovarian cancer metastases, for  potential translation tp patients with Stage III ovarian carcinoma.
Funding: COH, Anthony F. & Susan M. Markel Fund, NIH, The Rosalinde and Arthur Gilbert Foundation,  STOP Cancer, Alvarez Family Charitable Foundation. Ladies Auxillary Veteran’s Grant (R Mooney)
 
 
 
 
 
 
 
 
 
 
 
 
5. NSC Oncolytic Virotherapy
in collaboration with Maciej Lesniak laboratory, University of Chicago
Funding: NIH-U01 (PI, Lesniak)
 
We are further modifying our clinically relevant NSC line to produce conditionally replication competent oncolytic virus, CRAd-Survivan-pk7, for application to newly diagnosed glioma patients.
 

Translational Overview

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


Additional research investigations early in the pipeline include:
 
  • NSCs as a platform for production of anti-HER2 Antibody for application to HER2 positive breast cancer brain metastases.
  • Identification of factors involved in NSC-tumor tropism.
  • Investigating efficiency of NSC-tumor tropism following various routes of administration (intracranial, intravenous, intraperitoneal, intranasal).
 

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.

Neural Stem Cell-Mediated Cancer Treatment

Overview: Neural stem cells (NSCs) have a natural ability to home to malignant tumors and invasive tumor cells, making them an ideal delivery vehicle for transporting therapeutic agents to tumor sites.  Dr. Aboody and colleagues at COH were the first in the world to move this therapeutic strategy from “bench to bedside” for brain tumor patients, demonstrating safety of their NSCs. 
 
My translational research laboratory focuses on neural stem cells (NSCs) and their therapeutic applications for primary and metastatic tumors. Our novel findings have demonstrated the inherent tumor-tropic property of NSCs, and their use as cellular delivery vehicles to effectively target and deliver therapeutic payloads to invasive tumor sites, including brain tumors and metastatic cancers. Their capacity for tracking infiltrating tumor cells and localizing to distant micro-tumor foci make NSCs a novel and attractive tumor selective delivery vehicle with tremendous clinical potential. In effect, the NSCs serve as a platform for tumor-localized therapy, which should also minimize toxicity to normal tissues. Our current research focuses on modifying human NSCs to deliver different therapeutic agents to tumor sites in animal models.
 
Clinical Trials: In 2013, we completed a first in-human FDA approved safety/feasibility NSC clinical trial at City of Hope in patients with recurrent high-grade gliomas (clinical PI: Dr. Jana Portnow, MD).  The NSCs delivered an enzyme (cytosine deaminase; CD) that converts an inactive prodrug (5-flurocytosine; 5-FC) to an active chemotherapeutic agent (5-Flurouracil; 5-FU).  The 5-FU produced by the NSCs diffuses into surrounding brain tumor tissue, selectively killing dividing tumor cells.  By producing the chemo drug only at the tumor sites, systemic side effects are minimized.  Results of this study demonstrated: 1) safety of administering therapeutic NSCs into the brain tumor resection cavity or biopsy site; 2) proof of concept for tumor-localized chemotherapy production – demonstrating that the CD-expressing NSCs were able to convert oral 5-FC to the active chemo drug 5-FU, locally in the brain; and 3) no significant immune response following one round of treatment.  A phase I dose escalation, multi-treatment round study is currently accruing patients at COH.
 
Active Research
1. NSCs delivering a prodrug activating enzyme for tumor-localized chemotherapy production:   CD-NSCs + 5-FC → 5-FU
Funding: STOP Cancer, COH, The Rosalinde and Arthur Gilbert Foundation, The Ziman  Family  Foundation, NIH-NCI (Portnow, Aboody)
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
NSCs are genetically modified to express cytosine deaminase (CD).  When the inactive prodrug 5-FC is administered, it crosses the BBB and gets converted to the active chemotherapeutic 5-FU by the CD expressing NSCs locally at the brain tumor sites.  In effect, allowing for tumor localized chemotherapy production, and reducing toxic side effects to normal tissues.
 

2. NSCs delivering a prodrug activating enzyme for tumor-localized chemotherapy production:   CE-NSCs + IRN → SN-38
Funding:  California Institute of Regenerative Medicine, NIH-U01, The Rosalinde and Arthur Gilbert Foundation, STOP Cancer, Mary Kay Foundation (Berlin, Aboody)
 
NSC-mediated CE/Irinotecan (CPT-11) enzyme/prodrug therapy.  NSCs localize to metastatic tumor sites and express the CE enzyme. CE converts the intravenously administered CPT-11 (irinotecan) prodrug to the active chemotherapeutic drug SN-38.  SN-38 is highly toxic to the surrounding tumor cells
 
In 2010, we were granted an $18M CIRM Disease Team Award to move a 2nd generation enzyme/prodrug therapeutic toward clinical trials (Co-PIs:  Jana Portnow, MD and Larry Couture, PhD). Collaborators include the Synold lab for pharmacology, the Barish lab for 3D tumor reconstruction, the Forman lab (C Brown) for xenogen imaging and tumor modeling, and the Moats lab at Children’s Hospital Los Angeles for MRI imaging. We also work closely with the Center for Biomedicine & Genetics and the Office of IND Development and Regulatory Affairs. An IND has been submitted and we expect to initiate a phase I study for this NSC-mediated brain tumor therapy in 2015.  We are also funded $4.7M by an NIH-U01 (in collaboration with CHLA and St. Jude) to move this same product to clinical trial for pediatric patients with metastatic neuroblastoma by 2017.
 

3. NSCs delivering internalized gold nanoparticles for thermal ablative therapy
in collaboration with Jacob Berlin laboratory, COH
 
After loading NSCs with gold nanorods (NSC-AuNPs), they are administered (current preclinical investigations focusing on bladder and prostate cancer).  Following migration of NSCs to tumor  sites, localizing the gold particles, near infrared laser is applied, causing the gold nanoparticles to  vibrate and generate heat – ‘burning’ surrounding tumor tissue.
Funding:  COH, The Rosalinde and Arthur Gilbert Foundation, STOP Cancer, Alvarez Family  Charitable Foundation, Mary Kay Foundation (Berlin, Aboody), Ladies Auxiliary Veteran’s Grant (Mooney)
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
4. NSCs delivering external nanoparticles for small molecule drug delivery
in collaboration with Jacob Berlin laboratory, COH
   
In collaboration with Dr. Berlin we are constructing NSC-NP hybrids, where the NPs are being  constructed to release drug after NSCs reach the tumor.  The NPs will be externally bound to the  NSCs.  Our initial preclinical studies are focused on peritoneal ovarian cancer metastases, for  potential translation tp patients with Stage III ovarian carcinoma.
Funding: COH, Anthony F. & Susan M. Markel Fund, NIH, The Rosalinde and Arthur Gilbert Foundation,  STOP Cancer, Alvarez Family Charitable Foundation. Ladies Auxillary Veteran’s Grant (R Mooney)
 
 
 
 
 
 
 
 
 
 
 
 
5. NSC Oncolytic Virotherapy
in collaboration with Maciej Lesniak laboratory, University of Chicago
Funding: NIH-U01 (PI, Lesniak)
 
We are further modifying our clinically relevant NSC line to produce conditionally replication competent oncolytic virus, CRAd-Survivan-pk7, for application to newly diagnosed glioma patients.
 

Translational Overview

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


Additional research investigations early in the pipeline include:
 
  • NSCs as a platform for production of anti-HER2 Antibody for application to HER2 positive breast cancer brain metastases.
  • Identification of factors involved in NSC-tumor tropism.
  • Investigating efficiency of NSC-tumor tropism following various routes of administration (intracranial, intravenous, intraperitoneal, intranasal).
 

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
  • Karen Reckamp, M.D., M.S., has an office next to my own, and we often see patients at the same time. As such, I’ve gotten to know her quite well over the years, and I’ve also gotten a glimpse of many of her patients. She specializes in lung cancer, and most of her patients have tumors […]
  • Today is National Doctors Day, the official day to recognize, thank and celebrate the tremendous work physicians do each and every day. Launched in 1991 via a presidential proclamation from then-President George Bush, the observance offers a chance to reflect on the qualities that define truly great medical car...
  • When considering cancer risk, categories like “women’s cancers” and “men’s cancers” may not matter. A complete medical history, especially of first-degree relatives, must be considered when evaluating risk. A new study drives home that fact. Published in the journal Cancer, the study found a link between a fami...
  • Precision medicine holds promise – on that doctors, especially cancer specialists, can agree. But this sophisticated approach to treatment, which incorporates knowledge about a person’s genetic profile, environment and lifestyle, isn’t yet standard for all cancers. It can’t be. Researchers and scientists are st...
  • Frank Di Bella, 70, is on a mission: Find a cure for metastatic bladder cancer. It’s just possible he might. Although Di Bella isn’t a world-renowned physician, cancer researcher or scientist, he knows how to make things happen. For more than 20 years, he served as chairman of annual fundraising gal...
  • The physical side effects of cancer can damage anyone’s self-confidence, but especially that of women who, rightly or wrongly, are more likely to find their appearance (or their own perception of their appearance) directly connected to their ability to face the world with something resembling aplomb. Furt...
  • The promise of stem cell therapy has long been studied in laboratories. Now, as medicine enters an era in which this therapy will be increasingly available to patients, the nurses who help deliver it will be in the spotlight. City of Hope, which has launched its Alpha Clinic for Cell Therapy and Innovation (ACT...
  • Just because you can treat a condition, such as high cholesterol, at the end of life — well, that doesn’t mean you should. That’s the basic lesson of a study to be published March 30 in JAMA Internal Medicine. The ramifications go far beyond that. The research, in which City of Hope’s Betty Fe...
  • The understanding of the relationship between genetics and cancer risk continues to grow, with more genetic testing than ever before available to patients. However, the adage that a little knowledge is a dangerous thing is applicable: Without context for what a test result means, and without meaningful guidance...
  • Standard prostate biopsies haven’t changed significantly in the past 30 years – nor have the problems inherent with them. Regular biopsies have an expected error rate: Tumors may potentially be undersampled and, 30 percent of the time, men who undergo a radical prostatectomy are found to have more aggress...
  • In the field of cancer, patients have had surgery, chemotherapy and radiation therapy as options. Now, as City of Hope officially opens the Alpha Clinic for Cellular Therapy and Innovation, patients battling cancer and other life-threatening diseases have another option: stem-cell-based therapy. The Alpha Clini...
  • How does the environment affect our health? Specifically, how does it affect our risk of cancer? City of Hope physicians and researchers recently answered those questions in an Ask the Experts event in Corona, California, explaining the underlying facts about how the environment can affect our health. Moderator...
  • Nurses and other medical professionals have come to understand that it’s not enough just to fight disease. They also must provide pain relief, symptom control, and an unrelenting commitment to improve patients’ quality of life — especially at the end of life. Not too long ago, this was a relatively ...
  • “Tonight, I’m launching a new precision medicine initiative to bring us closer to curing diseases like cancer.” These were the words of President Barack Obama on Jan. 20, 2015, during his State of the Union address. So what is precision medicine, and how close are we to making it a reality for...
  • March is Colon Cancer Awareness Month. How sad, yet how serendipitous, that the co-creator of “The Simpsons” Sam Simon passed away in March after a four-year battle against colon cancer. What message can we all learn from his illness that can help us prevent and overcome colon cancer in our own lives? Colon can...