ADAGiO: Adoptive Cellular Therapy for the TreAtment of Recurrent OliGodendrogliOma (OG) Adult Patients

After screening consent, subjects will undergo standard of care resection or biopsy for confirmatory diagnosis of disease progression and aseptic collection of tumor material for DNA and RNA extraction and sequencing, amplification, and loading of autologous DCs. Following biopsy and confirmatory pathologic diagnosis, eligible patients will be enrolled in treatment. After surgery, patients will undergo a G-CSF mobilized pheresis to collect PBMCs for DC generation and CD34+ HSCs. Amplified tumor RNA obtained from surgically resected or biopsied specimens will be used to generate total tumor RNA-pulsed DCs (TTRNA-DCs) manufactured while patients initiate salvage chemotherapy regimen after surgery. Salvage chemotherapy with IDH1/2 inhibitor will initiate 1-2 weeks after G-CSF mobilized leukapheresis for 1-3 cycles after which, treatment cycles will be paused, and the patients will receive 3 priming TTRNA-DCs vaccines every 2 weeks and undergo a non-mobilized leukapheresis to collect vaccine-boosted lymphocytes for ex vivo T cell expansion and generation of additional TTRNA-DC vaccines. Treatment with IDH1/2 inhibitor will resume with monthly TTRNA-DC vaccines for an additional 1-3 cycles until ex vivo expanded T cells are manufactured. For ACT, patients will undergo non-myeloablative conditioning with cyclophosphamide /fludarabine. The total immunotherapy regimen will consist of up to 9 intradermal DC vaccines (three -bi-weekly (q2 weeks) for priming, monthly for additional 2-3 cycles during T cell expansion, and three bi-weekly during T cell engraftment), a single i.v. infusion of ex vivo expanded tumor-reactive T cells, and a i.v. single infusion of autologous HSCs. The duration of treatment from enrollment to completion of DLT window is anticipated to be 7 to 9 months.