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| Item Type: | Article |
|---|---|
| Title: | Multiomic and longitudinal dissection of immune dynamics associated with Parkinsonism after ciltacabtagene autoleucel therapy |
| Creators: |
Kadel, Sofie-Katrin, Scheller, Lukas, Leipold, Alexander M., Krammer, Tobias, Raskó, Tamás, Alb, Miriam, Weis, Philipp, Leberzammer, Maria, Schmitt, Friederike, Stetter, Clara, Tamamushi, Yoko, Köck, Alicia, Köberle, Philipp, Reich, Martin, Musacchio, Thomas, Doppler, Kathrin, Sommer, Claudia, Cebulla, Nadine, McFleder, Rhonda, Ip, Chi Wang, Volkmann, Jens, Kallius, Matthias, Serfling, Sebastian E., Hartrampf, Philipp E., Buck, Andreas K., Pande, Amit  ORCID: https://orcid.org/0009-0008-0826-973X, Löffler, Dennis, Gernert, Michael, Duell, Johannes, Topp, Max S., Mersi, Julia, Waldschmidt, Johannes, Einsele, Hermann, Hudecek, Michael, Saliba, Antoine-Emmanuel, Rasche, Leo and Kortüm, K. Martin
|
| Abstract: | We report a fatal case of parkinsonism following treatment with ciltacabtagene autoleucel (cilta-cel). To investigate underlying mechanisms, we performed a multipronged longitudinal analysis using single-cell RNA (scRNA)/T-cell receptor (TCR) sequencing, flow cytometry, and cytokine measurements including cerebrospinal fluid (CSF) and peripheral blood (PB) samples, spanning more than 6 months after chimeric antigen receptor (CAR) T-cell therapy. Combined clinical and molecular findings revealed a biphasic immunologic process in the CSF. The early phase was characterized by a selective influx of predominantly CD4(+) CAR T cells, accompanied by the evidence of endothelial dysfunction, prior to the clinical manifestation of parkinsonism. A second phase was preceded by a locally restricted inflammatory process in the CSF. Subsequently, an increase in the CSF to serum albumin ratio indicated disruption of the blood–brain barrier, coinciding with a pronounced influx of T cells—primarily CAR T cells but also clonally expanded, cytotoxic CD8(+) non-CAR T cells—which was associated with neuronal injury and clinical decline. SIGNIFICANCE: This article examines central nervous system immune dynamics in a patient developing parkinsonism after cilta-cel. A longitudinal real-world dataset of CSF (n = 8) and PB (n = 6) from six matched time points was analyzed using scRNA/TCR sequencing over 6 months, capturing disease onset and progression. |
| Keywords: | Adoptive Immunotherapy, Chimeric Antigen Receptors, Longitudinal Studies, Multiomics, Parkinsonian Disorders |
| Source: | Blood Cancer Discovery |
| ISSN: | 2643-3230 |
| Publisher: | American Association for Cancer Research |
| Volume: | 7 |
| Number: | 4 |
| Page Range: | 544-557 |
| Date: | 1 July 2026 |
| Official Publication: | https://doi.org/10.1158/2643-3230.bcd-25-0278 |
| PubMed: | View item in PubMed |
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