# Brain-Imaging Markers of Neurotoxicity and Long-Term Outcomes after CAR-T Cell Therapy

> **NIH CA R01** · CHILDREN'S HOSPITAL OF LOS ANGELES · 2026 · $702,424

## Abstract

Project Summary
CD19-directed chimeric antigen receptor (CAR)-T cell therapy for relapsed or refractory B-cell acute
lymphoblastic leukemia (ALL) induces complete remission in 70-90% of otherwise incurable patients. CAR-T
cell engagement with their target antigens induces expansion of activated CAR-T cells, producing cytokines
and other pro-inflammatory mediators. Unfortunately, in approximately 50% of patients this inflammatory
response also produces an Immune effector Cell-Associated Neurotoxicity Syndrome (ICANS), a serious
neurotoxicity characterized by delirium, encephalopathy, dysphasia, and in severe cases, diffuse cerebral
edema that can be fatal. Additionally, ICANS increases the risk for long-term cognitive impairments; possible
consequences that have not been systematically studied. ICANS therefore remains a major challenge for the
wider adoption of CAR-T cell therapy, creating an urgent need to mitigate or prevent ICANS, to understand its
pathophysiology, and to predict its adverse long-term outcomes. We have compelling preliminary data
demonstrating that several pre-infusion neuroimaging markers predict ICANS with high accuracy. Building
upon these findings, we will develop a predictive algorithm in this proposal that will facilitate closer monitoring
of high-risk patients, support with preventive treatments, and risk-adapted dosing of CAR-T cells. Our
preliminary data also suggest that neuroimaging biomarkers serve as objective surrogates for clinical and
subclinical ICANS. These markers may guide future development of targeted anti-cytokine and small molecule
inhibitor-based interventions to inhibit or block neurotoxicity-specific pathways. Finally, preliminary data support
our hypothesis that ICANS-induced abnormalities in attentional networks of the brain cause long-term
neurocognitive impairments. Adverse outcomes are also seen in low grade neurotoxicity, suggesting a greater
need than previously anticipated for cognitive and behavioral interventio

## Key facts

- **NIH application ID:** 11301859
- **Project number:** 5R01CA274137-04
- **Recipient organization:** CHILDREN'S HOSPITAL OF LOS ANGELES
- **Principal Investigator:** Ravi  Bansal; Deepa  Bhojwani; BRADLEY S PETERSON
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** CA
- **Fiscal year:** 2026
- **Award amount:** $702,424
- **Award type:** 5
- **Project period:** 2023-04-01T00:00:00 → 2028-03-31T00:00:00

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11301859

## Citation

> US National Institutes of Health, RePORTER application 11301859, Brain-Imaging Markers of Neurotoxicity and Long-Term Outcomes after CAR-T Cell Therapy (5R01CA274137-04). Retrieved via AI Analytics 2026-06-26 from https://api.ai-analytics.org/grant/nih/11301859. Licensed CC0.

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