Brain Cancer Research Supported by New Ivy Foundation Grant

September 22, 2017 | by Katie Neith

Aboody 256x256 Karen Aboody, M.D.
Glioblastoma is a cancer of the brain that is difficult to treat and has a high recurrence rate. Thanks to funding from the Ben & Catherine Ivy Foundation, City of Hope researchers are advancing their work against this aggressive and often-fatal cancer.
The Ben & Catherine Ivy Foundation aims to cure brain cancer by funding leading-edge research that will improve diagnostics and treatment options. Karen Aboody, M.D., professor in the Department of Developmental and Stem Cell Biology and Division of Neurosurgery, received a $1.5 million three-year grant from the organization for her work that employs neural stem cells (NSCs) and oncolytic viruses to destroy invasive brain tumors.
Glioblastoma is difficult to treat for numerous reasons, including invasive cells that escape a surgical margin, and the blood-brain barrier, which blocks systemically administered therapies from getting to the brain.
Aboody and her team have found a way to overcome these obstacles by using tumor-homing NSCs as carriers for anti-cancer treatments. The NSCs can target and penetrate brain tumor sites throughout the brain, localizing the anti-cancer treatment selectively to tumor cells and therefore minimizing toxic side effects to normal tissues. 
After initiating two first-in-human glioma trials with NSC chemotherapies, Aboody is now planning to use these NSCs to deliver oncolytic viruses, which infect and amplify their killing effect on cancer cells. Dubbed “NSC oncolytic virotherapy,” this approach has the potential to be an effective novel treatment for newly diagnosed and recurrent glioma patients, with potential use in pediatric and metastatic brain tumors as well.
Funding from the Ivy Foundation will support both preclinical translational studies and a phase 1 clinical trial and of NSC oncolytic virotherapy. The laboratory studies will be led by Aboody, with staff scientist Rachael Mooney, Ph.D., and graduate student Jennifer Batalla. Collaborating investigator David Curiel, M.D., Ph.D., from Washington University, is also contributing expertise to develop novel and improved NSC oncolytic virotherapies for brain tumors, potentially in combination with immunotherapy.
The clinical trial at City of Hope will be led by Jana Portnow, M.D., associate director of the Brain Tumor Program. The clinical trial was also recently initiated at Northwestern University, led by collaborator Maciej Lesniak, M.D.
“Our overall goal is to significantly improve clinical outcomes for patients with glioma and minimize treatment side effects, using neural stem cells to target oncolytic virotherapy specifically to tumor sites,” said Aboody. “This generous grant supports research development of additional NSC oncolytic virotherapy approaches and enables us to conduct a novel clinical trial of NSC oncolytic virotherapy for newly diagnosed glioma patients at City of Hope.” 
Christine Brown | City of Hope Christine Brown, Ph.D.
Christine Brown, Ph.D., City of Hope’s Heritage Provider Network Professor in Immunotherapy, is also working toward a more effective therapy for glioblastomas.
As associate director of the T Cell Therapeutics Research Laboratory, she oversees an ongoing clinical trial program focused on the development of chimeric antigen receptor (CAR)-engineered T cells for the treatment of hematological malignancies and solid tumors. Brown’s $1.5 million three-year grant from the Ivy Foundation will support her research efforts using CAR T cells for the treatment of malignant brain tumors.  
This type of immunotherapy - which uses modified versions of a patient’s own cells — is emerging as a promising strategy to treat cancer. In fact, in recent clinical trials done by Brown and colleagues, the results demonstrated safety and antitumor activity for a CAR T cell therapy developed at City of Hope for treating glioblastomas.  
However, glioblastoma often returns with tumors that are resistant to therapy. Brown’s new research builds on what her group has learned from clinical trials and may offer new therapeutic options for patients diagnosed with drug-resistant brain tumors.
Brown thinks that tumor relapse after CAR T cell therapy is likely due to the immunotherapy not targeting enough of the initial tumor cells and could be reduced by engineering CAR T cells that recognize the widest range of glioblastoma cells. Brown hopes to test this hypothesis by developing CARs that target broadly expressed tumor antigens, and by designing a dual-targeted CAR that recognizes two cell surface receptors highly expressed on brain tumor cells.

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