Lymphodepletion mitigates anti-CAR immunity in pediatric and young adult patients with recurrent or refractory brain tumors: clinical trial results
- 1City of Hope National Medical Center
Abstract
Outcomes for high-grade pediatric brain tumor patients remain poor, but there is optimism that chimeric antigen receptor (CAR) T cell therapy can improve prognosis. We present the results from a phase I clinical trial of IL13BB{zeta}-CAR T cells infused weekly into the cerebral ventricles in pediatric and young adult patients with recurrent or refractory brain tumors. The trial met its primary objectives of feasibility, safety, and tolerability, with one dose-limiting toxicity. 8 of 16 patients evaluable for response experienced radiographic size decreases consistent with biologic activity and with an anti-tumor response. Two patients met protocol criteria for response. Median survival for patients receiving lymphodepletion was 20.5 months from diagnosis and 6.9 months from treatment for patients with midline glioma, and 187 months from diagnosis and 7.5 months from treatment for patients with ependymoma. Importantly, patients who did not receive lymphodepletion developed anti-CAR humoral and cellular immune responses detectable in the CSF and peripheral blood, whereas patients receiving lymphodepletion had no evidence of CSF anti-CAR immunity. Taken together, these findings demonstrate the safety, tolerability, and biological activity of locoregionally-delivered IL13BB{zeta}-CAR T cells for children and young adults with CNS tumors. Moreover, we show that anti-CAR immune responses arise in patients not receiving lymphodepletion, but not in the CSF of patients receiving systemic lymphodepletion. Further investigation of adoptive cellular therapies combined with immunosuppression is warranted in this patient population. ClinicalTrials.gov registration: NCT04510051.
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BibTeX
@misc{wang2026lymphodepletion,
title = {{Lymphodepletion mitigates anti-CAR immunity in pediatric and young adult patients with recurrent or refractory brain tumors: clinical trial results}},
author = {L. D. Wang and A. M. T. Oill and S. E. Lindner and T. Stiller and C. Egelston and M. S. Blanchard and R. Mudunuri and J. C. Hibbard and M. Wu and S. M. Sepulveda and L. Peter and J. L. Kilpatrick and J. Stratman and E. D. Mee and D. G. Chen and G. Oliveira and M. Munoz and A. Burmayan and J. Wagner and A. M. Dolatabadi and M. Nisis and J. K. Shepphird and G. Sanchez and H. M. Natri and C. Oliver-Cervantes and L. Feldman and M. Aftabizadeh and L. Arvanitis and K. M. Campbell and J. A. Cotter and J. A. Read and J. A. Read and S. Shahani and S. J. Forman and T. Adam and D. de la Nava Martin and S. A. Richman and J. Paul and J. Wadden and B. Badie and B. Tamrazi and Koschmann},
howpublished = {medRxiv},
year = {2026},
month = aug,
doi = {10.64898/2026.08.27.26361261},
url = {https://www.medrxiv.org/content/10.64898/2026.08.27.26361261v1},
note = {CC BY-NC},
}
RIS
TY - UNPB
TI - Lymphodepletion mitigates anti-CAR immunity in pediatric and young adult patients with recurrent or refractory brain tumors: clinical trial results
AU - L. D. Wang
AU - A. M. T. Oill
AU - S. E. Lindner
AU - T. Stiller
AU - C. Egelston
AU - M. S. Blanchard
AU - R. Mudunuri
AU - J. C. Hibbard
AU - M. Wu
AU - S. M. Sepulveda
AU - L. Peter
AU - J. L. Kilpatrick
AU - J. Stratman
AU - E. D. Mee
AU - D. G. Chen
AU - G. Oliveira
AU - M. Munoz
AU - A. Burmayan
AU - J. Wagner
AU - A. M. Dolatabadi
AU - M. Nisis
AU - J. K. Shepphird
AU - G. Sanchez
AU - H. M. Natri
AU - C. Oliver-Cervantes
AU - L. Feldman
AU - M. Aftabizadeh
AU - L. Arvanitis
AU - K. M. Campbell
AU - J. A. Cotter
AU - J. A. Read
AU - J. A. Read
AU - S. Shahani
AU - S. J. Forman
AU - T. Adam
AU - D. de la Nava Martin
AU - S. A. Richman
AU - J. Paul
AU - J. Wadden
AU - B. Badie
AU - B. Tamrazi
AU - Koschmann
PY - 2026
DA - 2026/08/27
PB - medRxiv
DO - 10.64898/2026.08.27.26361261
UR - https://www.medrxiv.org/content/10.64898/2026.08.27.26361261v1
AB - Outcomes for high-grade pediatric brain tumor patients remain poor, but there is optimism that chimeric antigen receptor (CAR) T cell therapy can improve prognosis. We present the results from a phase I clinical trial of IL13BB{zeta}-CAR T cells infused weekly into the cerebral ventricles in pediatric and young adult patients with recurrent or refractory brain tumors. The trial met its primary objectives of feasibility, safety, and tolerability, with one dose-limiting toxicity. 8 of 16 patients evaluable for response experienced radiographic size decreases consistent with biologic activity and with an anti-tumor response. Two patients met protocol criteria for response. Median survival for patients receiving lymphodepletion was 20.5 months from diagnosis and 6.9 months from treatment for patients with midline glioma, and 187 months from diagnosis and 7.5 months from treatment for patients with ependymoma. Importantly, patients who did not receive lymphodepletion developed anti-CAR humoral and cellular immune responses detectable in the CSF and peripheral blood, whereas patients receiving lymphodepletion had no evidence of CSF anti-CAR immunity. Taken together, these findings demonstrate the safety, tolerability, and biological activity of locoregionally-delivered IL13BB{zeta}-CAR T cells for children and young adults with CNS tumors. Moreover, we show that anti-CAR immune responses arise in patients not receiving lymphodepletion, but not in the CSF of patients receiving systemic lymphodepletion. Further investigation of adoptive cellular therapies combined with immunosuppression is warranted in this patient population. ClinicalTrials.gov registration: NCT04510051.
ER -