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Background <p>Chimeric antigen receptor (CAR) T cell therapy has revolutionized treatment for hematologic malignanciesand is now being applied to central nervous system (CNS) tumors. As experience grows, distinct neurotoxicities are emerging that differ from those observed in systemic CAR T cell therapy. Understanding these toxicities is critical for optimizing safety and advancing clinical translation.</p> Methods <p>We reviewed preclinical data and early-phase clinical trials of CAR T cell therapy for CNS tumors, focusing on the characterization, mechanisms, and management of treatment-associated neurotoxicity. Three major categories were examined: immune effector cell–associated neurotoxicity syndrome (ICANS), tumorinflammation–associated neurotoxicity (TIAN), and other non-ICANS neurotoxicities (NINTs), including movement and neurocognitive treatment-emergent events.</p> Results <p>ICANS reflects a global, cytokine-mediated process, whereas TIAN represents localized inflammation at the tumor site, producing either mechanical (type 1) or electrophysiologic (type 2) neurologic dysfunction. TIAN is common across phase I trials of locoregional CAR T cell therapy for CNS tumors, often transient and reversible, and may require corticosteroids, IL-1 blockade, or cerebrospinal fluid diversion. ICANS remains uncommon in this setting. Emerging data also suggest microglial activation and neurocognitive effects paralleling chemotherapy-related cognitive impairment.</p> Conclusion <p>CAR T cell therapy for CNS tumors induces unique neurotoxicities reflecting local immune activation within the brain. Differentiating ICANS from TIAN is essential for appropriate management. Standardized grading criteria, prospective neurocognitive monitoring, and rational CAR design are critical next steps in safely advancing CAR T cell therapy in neuro-oncology.</p>

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Neurotoxicity in central nervous system tumors treated with CAR T cell therapy: a review

  • 期刊论文

  • 发表日期：

    2025年10月31日

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  • Jasia Mahdi,
  • Juliane A. Gust,
  • Nicholas A. Vitanza,
  • Brian Scott,
  • Michelle Monje,
  • Rebecca Ronsley

摘要

Background

Chimeric antigen receptor (CAR) T cell therapy has revolutionized treatment for hematologic malignanciesand is now being applied to central nervous system (CNS) tumors. As experience grows, distinct neurotoxicities are emerging that differ from those observed in systemic CAR T cell therapy. Understanding these toxicities is critical for optimizing safety and advancing clinical translation.

Methods

We reviewed preclinical data and early-phase clinical trials of CAR T cell therapy for CNS tumors, focusing on the characterization, mechanisms, and management of treatment-associated neurotoxicity. Three major categories were examined: immune effector cell–associated neurotoxicity syndrome (ICANS), tumorinflammation–associated neurotoxicity (TIAN), and other non-ICANS neurotoxicities (NINTs), including movement and neurocognitive treatment-emergent events.

Results

ICANS reflects a global, cytokine-mediated process, whereas TIAN represents localized inflammation at the tumor site, producing either mechanical (type 1) or electrophysiologic (type 2) neurologic dysfunction. TIAN is common across phase I trials of locoregional CAR T cell therapy for CNS tumors, often transient and reversible, and may require corticosteroids, IL-1 blockade, or cerebrospinal fluid diversion. ICANS remains uncommon in this setting. Emerging data also suggest microglial activation and neurocognitive effects paralleling chemotherapy-related cognitive impairment.

Conclusion

CAR T cell therapy for CNS tumors induces unique neurotoxicities reflecting local immune activation within the brain. Differentiating ICANS from TIAN is essential for appropriate management. Standardized grading criteria, prospective neurocognitive monitoring, and rational CAR design are critical next steps in safely advancing CAR T cell therapy in neuro-oncology.