Details

Autor(en) / Beteiligte

• Davidson, Tom
• Oill, Angela
• Wu, Melody
• Egelston, Colt
• Natri, Heini
• Sepulveda, Sean
• Hibbard, Jonathan
• Wagner, Jamie
• Nisis, Monica
• Kilpatrick, Julie
• Stiller, Tracey
• Georges, Joseph
• Munoz, Margarita
• Oliver-Cervantes, Cheryl
• Shepphird, Jennifer
• Ressler, Julie
• D’Apuzzo, Massimo
• Aftabizadeh, Maryam
• Blanchard, M Suzette
• Badie, Behnam
• Brown, Christine
• Banovich, Nicholas
• Wang, Leo

Titel

TRLS-05. PRELIMINARY RESULTS FROM A PHASE I TRIAL TO EVALUATE INTRAVENTRICULAR DELIVERY OF IL13RΑ2-TARGETING CAR T CELLS AFTER LYMPHODEPLETION IN PEDIATRIC BRAIN TUMORS PATIENTS

Ist Teil von

• Neuro-oncology (Charlottesville, Va.), 2023-06, Vol.25 (Supplement_1), p.i79-i80

Ort / Verlag

US: Oxford University Press

Erscheinungsjahr

2023

Link zum Volltext

Quelle

Oxford Journals 2020 Medicine

Beschreibungen/Notizen

• Abstract Brain tumors are the leading cause of cancer death in children, and outcomes for patients with recurrent or aggressive disease remain poor. We have previously shown that locoregionally-delivered chimeric antigen receptor (CAR) T cells targeting the high-affinity IL13 receptor IL13Rα2 are safe and well-tolerated in adults, and that they can mediate a remarkable clinical response. This antigen is also expressed on roughly half of pediatric neuromalignancies. Here, we present the clinical experience from the first patients treated with IL13BBζ-CAR T cells on our trial. Patients received four doses of CAR T cells, delivered weekly through an indwelling CNS catheter; the first dose was 1e7 CAR T cells and subsequent doses were 5e7 cells. The first three patients received CAR T cells alone; the rest received lymphodepletion with cyclophosphamide and fludarabine before CAR T cell infusion. After follow-up imaging at the end of the dose-limiting toxicity (DLT) period, patients were given the option to continue therapy. Six patients have been treated without DLTs; one patient on the lymphodepletion arm did not complete the four infusions due to a Grade 3 catheter-related infection. Other patients experienced occasional Grade 3 AEs that were not attributed to CAR T therapy, with the exception of headache, muscle weakness, and ALT elevation. Otherwise, AEs were Grade 1-2. Five patients completed four infusions and were evaluable at the end of the DLT period. Of those, three experienced radiographic and/or clinical benefit, although none met protocol criteria for a partial response. Specific cytokines were increased in the cerebrospinal fluid (CSF) of patients during radiographic response periods. Additionally, single-cell transcriptomic analysis paired with TCR sequencing of CSF cells demonstrated characteristic immune signatures correlated with response. These preliminary results support combining lymphodepletion and repeated intraventricular CAR T cell delivery as a promising therapy in children with brain tumors.