Lymphodepletion mitigates anti-CAR immunity in pediatric and young adult patients with recurrent or refractory brain tumors: clinical trial results
Year: 2026
Type: preprint
Study design: Clinical Trial
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 IL13BBζ-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 IL13BBζ-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 .
Source: medRxiv
Authors: Leo D. Wang, Angela M. Taravella Oill, Silke E. Lindner, Tracey Stiller, M. Suzette Blanchard, Rishika V. Mudunuri, Melody Wu, Jonathan C. Hibbard, Colt Egelston, Sean M. Sepulveda, Lance Peter, Julie L. Kilpatrick, Jennifer Stratman, Evan D. Mee, Daniel G. Chen, Giacomo Oliveira, Margarita Muñoz, Jamie Wagner, Ally Mardiroos Dolatabadi, Monica Nisis, Jennifer K. Shepphird, Gabriela Sanchez, Angela Burmayan, Kiana Langeliers, Jinny Paul, Yolanda Villasenor, Jack Wadden, Tiffany Adam, Daniel de la Nava, Heini M. Natri, Cheryl Oliver-Cervantes, Lisa Feldman, Shilpa Shahani, Maryam Aftabizadeh, Stephen J. Forman, Julie Ressler, Leonidas Arvanitis, Katie M. Campbell, Jennifer A. Cotter, Sarah A. Richman, Massimo D’Apuzzo, Benita Tamrazi, Behnam Badie, Catherine J. Wu, Jay A. Read, Santhosh A. Upadhyaya, Carl Koschmann, Tom B. Davidson, Nicholas E. Banovich, Christine E. Brown
Institutions: City Of Hope National Medical Center, City of Hope, Beckman Research Institute, Translational Genomics Research Institute, University of California, Los Angeles, UCLA Jonsson Comprehensive Cancer Center, Dana-Farber Cancer Institute, University of Michigan, Michigan Medicine, University of Southern California, Children's Hospital of Los Angeles
Topic: CAR-T cell therapy research
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: green
Awards: G1094731811, G155444459, G201291728, G4372315411, The City of Hope Alpha Clinic: A roadmap for improving access to regenerative medicine therapies for all Californians, Phase I Study of IL13Rα2-Targeting CAR T Cells After Lymphodepletion for Children with Refractory or Recurrent Malignant Brain Tumors
OpenAlex ID: W7204939178