Alliance for Cancer Gene Therapy (ACGT) has awarded a collaboration research grant supporting the team effort of scientists at three academic institutions to develop a cell and gene therapy for pediatric brain tumors. Cell and gene therapy harnesses the power of the immune system to destroy cancer cells while not harming healthy tissue.
The ACGT-Barbara Netter Fund Collaboration Challenge Award has been awarded to Stephen Gottschalk, MD (St. Jude Children’s Research Hospital), Crystal Mackall, MD (Stanford University), and Sheila Singh, MD, PhD (McMaster University Cancer Research Centre). This team of researchers are leading a multi-institutional collaboration titled “Synthetic T-cell therapy against recurrent pediatric brain tumors (STAR)” that focuses on the pediatric brain tumors medulloblastoma and ependymoma.
Medulloblastoma, which develops in the lower back part of the brain, is the most common type of cancerous brain tumor in children. Approximately 500 children are diagnosed in the United States each year.
Ependymoma forms from ependymal cells, which are in the ventricles of the brain and the central canal of the spinal cord. Approximately 250 children in the United States are diagnosed each year.
The ACGT-Barbara Netter Fund Collaboration Challenge Award will support pre-clinical testing of a new T-cell therapy in preparation for a phase 1 clinical trial.
What is ‘synthetic’ T-cell therapy?
The synthetic T-cell therapy developed by Drs. Gottschalk, Mackall and Singh requires genetic engineering of T cells to target cancer cells.
There are six T-cell therapies approved to treat blood cancers such as leukemia, lymphoma and multiple myeloma. These therapies, called CAR T-cell therapies, use one genetic modification to the T cells to target cancer.
Brain tumors have unique obstacles, such as an immunosuppressive environment and a barrier separating the blood and the brain. These obstacles can prevent CAR T cells from reaching the brain or penetrating through the tumor wall.
The synthetic T cells in the STAR research program have several genetic modifications to make them more persistent.
“It’s almost like we are training these cells to be Olympic athletes,” Dr. Singh says. “You can train the T cells with genetic engineering to jump higher and run faster. Dr. Gottschalk’s gene edit is like training someone to be a hurdler. It allows the T cells to jump over the immunosuppressive environment around the brain. Dr. Mackall’s gene edit is like training to make the cells run faster without getting as tired.”
What are the challenges of treating pediatric brain tumors?
Drs. Gottschalk, Mackall and Singh are focusing their research on pediatric brain tumors due to the complexities of treating these diseases. In medulloblastoma, the tumor originates in an area of the brain still developing for children. While chemotherapy puts the disease in remission for 70-80% of cases, cancer cells can evade treatment and continue to multiply as the brain develops. For these children – and the other 20-30% whose tumors did not respond to chemotherapy – there are no therapeutic options.
The same is true for children with ependymoma.
“The timing of the ACGT-Barbara Netter Fund Collaboration Challenge Award was perfect because our collaboration was already germinating,” Dr. Mackall says. “This group is committed to working together for the long haul for this patient population.”
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