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| Item Type: | Article |
|---|---|
| Title: | Multiomic and longitudinal dissection of immune dynamics associated with Parkinsonism after ciltacabtagene autoleucel therapy |
| Creators Name: | 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, 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. To investigate underlying mechanisms, we performed a multi-pronged longitudinal analysis using single-cell RNA/TCR sequencing, flow cytometry, and cytokine measurements including cerebrospinal fluid (CSF) and peripheral blood samples, spanning a time over 6 months after 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 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, a rise in the CSF/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. STATEMENT OF SIGNIFICANCE: This manuscript examines central nervous system immune dynamics in a patient developing parkinsonism after ciltacabtagene autoleucel. A longitudinal real-world dataset of cerebrospinal fluid (n = 8) and peripheral blood (n = 6) from six matched timepoints was analysed using single-cell RNA/TCR sequencing over six months, capturing disease onset and progression. |
| Source: | Blood Cancer Discovery |
| ISSN: | 2643-3230 |
| Publisher: | American Association for Cancer Research |
| Date: | 26 March 2026 |
| Official Publication: | https://doi.org/10.1158/2643-3230.bcd-25-0278 |
| PubMed: | View item in PubMed |
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