Genetically Engineered T Cells as Therapy for Pediatric Glioma
The intent of this project is to develop antigen-specific T cells as an effective immunotherapy for high grade glioma, a type of brain tumor that is largely resistant to conventional therapies resulting in poor outcomes. Using the patient's own immune system to fight cancers is one promising approach to improve outcomes for pediatric cancer patients who do not benefit from current therapies. However, the body's immune defenses against cancers often fail because the cancers do not induce or actively inhibit immunity. Cancer treatments consisting of the infusion of T cells that recognize tumor antigens, a molecule present on many cancers, have shown promise in early clinical studies.
We have now developed such an approach for patients with high grade glioma. In our approach we target a molecule called IL13Ra2, which is present on glioma cells. We have generated IL13Ra2-specific
T cells with a genetic approach and have shown that these cells have anti-glioma activity in pre-clinical models.
In this project, we now propose to optimize our IL13Ra2-targeted approach for high grade glioma. In Aim 1, we will evaluate if adding an additional gene to T cells that provides a growth factor called IL-15 can further enhance the anti-glioma activity of our IL13Ra2-specific T cells. In Aim 2, we will then explore if targeting an additional antigen called EphA2 on glioma cells further enhances anti-glioma effects. If our pre-clinical approach is successful and a clinical study is justified, we have the 'set-up in place' to develop such a study at our center.
"The Young Investigator Award from ALSF will allow me to perform the proposed studies at CAGT and TXCH, two centers that have a strong track record of training and equipping translational researchers and physician scientists. Thus, this award would bring me one step closer to my long-term goal of becoming an independent investigator with a strong translational focus on cancer immunotherapy for pediatric solid tumors and brain tumors." - Giedre Krenciute, PhD