CAR T Cell Receptor Immunotherapy Targeting EGFRvIII for Patients With Malignant Gliomas Expressing EGFRvIII

BACKGROUND: \- Patients with recurrent gliomas have very limited treatment options. Epidermal growth factor receptor (EGFR). (EGFRvIII) is the most common mutant variant of EGFR and is present in 24-67% of patients with glioblastoma. * EGFRvIII expression promotes oncogenesis and is associated with poor prognosis. * EGFRvIII is not expressed in normal tissue and is an attractive target for immunotherapy. * We have constructed a retroviral vector that contains a chimeric antigen receptor (CAR) that recognizes the EGFRvIII tumor antigen, which can be used to mediate genetic transfer of this CAR with high efficiency without the need to perform any selection. OBJECTIVES: Primary Objectives * To evaluate the safety of the administration of anti-EGFRvIII CAR engineered peripheral blood lymphocytes in patients receiving the non-myeloablative, lymphodepleting preparative regimen and aldesleukin. * Determine the six month progression free survival of patients receiving anti-EGFRvIII CAR-engineered peripheral blood lymphocytes and aldesleukin following a nonmyeloablative, lymphodepleting preparative regimen. ELIGIBILITY: * Histologically proven glioblastoma or gliosarcoma expressing EGFRvIII as determined by immunohistochemistry (IHC) or Reverse transcription polymerase chain reaction (RT-PCR) * Failed prior standard treatment with radiotherapy with or without chemotherapy * Karnofsky performance score (KPS) greater than or equal to 60 * Cardiac, pulmonary and laboratory parameters within acceptable limits DESIGN: * The study will be conducted using a Phase I/II design. * Patients will receive a non-myeloablative, lymphodepleting preparative regimen consisting of cyclophosphamide and fludarabine followed by intravenous infusion of ex vivo tumorreactive, CAR gene-transduced peripheral blood mononuclear cells (PBMC), plus intravenous (IV) aldesleukin. * Once the maximum tolerated cell dose (MTD) has been determined, the study will proceed to the phase II portion. * In the phase II portion of the trial, patients will be accrued to two cohorts: * Patients with recurrent malignant glioma receiving steroids at the time of treatment. * Patients with recurrent malignant glioma not receiving steroids at the time of treatment. * A total of 107 patients may be enrolled over a period of 7 years.