Dr. Christine Brown
Organization: City of Hope
A Phase I/II Trial of 8-Chloro-adenosine in Relapsed or Refractory Acute Myeloid Leukemia
Funding Year: 2017
Project period: 4 years
A Phase I Immunotherapy Study Using HER2-CAR T Cells for Malignant Glioma
The central hypothesis is that CAR T cells targeting cell surface antigens will eradicate diffuse tumor cell populations. This hypothesis will be tested in phase I clinical trial in 11 patients over a duration of four years. The study will assess the safety and determine the recommended phase II dosing plan for loco-regional administration in 3 routes.
High-grade malignant glioma (MG), including glioblastoma multiforme (GBM-grade IV), presents obstacles that have blocked attempts to improve patient outcomes—the five-year overall survival rate of patients with GBM is just 5.5%. In the majority of cases, standard therapies are not effective in eliminating malignant GBM cells, which spread microscopically throughout the brain. Long-term disease control requires therapy that targets and eliminates diffusely located cancer cells, and this represents an unmet medical need. Chimeric antigen receptor (CAR)–engineered T cells may provide a safe and effective way to treat MG. In this patient-specific immunotherapy, the patient’s T cells are isolated and engineered to specifically target tumor cells. We have developed a CAR T cell therapy for MG that targets human epidermal growth factor receptor 2 (HER2), which is found on a high percentage of MG tumors, but not on normal brain cells. Our central hypothesis is that CAR T cells targeting the cell surface specific to MG will eradicate cell populations in patients with MG. Thus far, 15 patients have received HER2-CAR T cells, 14 have completed the standard prescription of three doses with no adverse reactions, 10 patients have gone on to receive additional optional doses, and four patients remain on study awaiting CAR T cell infusion. This treatment is significant as it addresses the poor outcomes of patients with MG, and the findings may contribute to improved safety and effectiveness of CAR T cell therapy in brain and other cancers.