Multiomic and Longitudinal Dissection of Immune Dynamics Associated with Parkinsonism after Ciltacabtagene Autoleucel Therapy
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.
Authors
- Lukas Scheller (ORCID: https://orcid.org/0000-0002-0912-1808)
- M. Gernert
- Alexander M. Leipold (ORCID: https://orcid.org/0000-0002-9471-3276)
- Claudia Sommer (ORCID: https://orcid.org/0000-0002-7064-5002)
- Philipp E. Hartrampf (ORCID: https://orcid.org/0000-0001-5622-9849)
- Dennis Löffler
- Tamás Raskó
- Andreas K. Buck (ORCID: https://orcid.org/0000-0002-6447-0613)
- Sebastian E. Serfling (ORCID: https://orcid.org/0009-0001-5740-0537)
- Martin M. Reich (ORCID: https://orcid.org/0000-0001-9115-5136)
- Rhonda L. McFleder (ORCID: https://orcid.org/0000-0001-9986-4201)
- Kathrin Doppler (ORCID: https://orcid.org/0000-0003-2883-0009)
- Thomas Musacchio (ORCID: https://orcid.org/0000-0001-8416-4106)
- Philipp Weis
- Nadine Cebulla (ORCID: https://orcid.org/0000-0002-2376-2281)
- Tobias Krammer (ORCID: https://orcid.org/0000-0002-7638-9476)
- Matthias Kallius
- Johannes M. Waldschmidt (ORCID: https://orcid.org/0000-0001-5340-1818)
- Julia Mersi (ORCID: https://orcid.org/0009-0008-7651-8080)
- H Einsele
- Fabian Schmitt
- Jens Volkmann (ORCID: https://orcid.org/0000-0002-9570-593X)
- Maria Leberzammer
- Amit Pande (ORCID: https://orcid.org/0000-0001-5379-4746)
- Leo Rasche
- Yoko Tamamushi
- Philipp Köberle
- Clara Stetter
- C. W. Ip
- Antoine-Emmanuel Saliba
- Alicia Köck
- Miriam Alb
- Michael Hudecek
- Max S. Topp
- Johannes Duell
- Sofie-Katrin Kadel
- K Martin Kortüm
Institutions
- Max Delbrück Center (DE)
- University of Würzburg (DE)
- Universitätsklinikum Würzburg (DE)
- Fraunhofer Institute for Cell Therapy and Immunology (DE)
- Technical University of Munich (DE)
Publication Details
- Journal
- Blood Cancer Discovery
- Published
- 2026-03-26
- DOI
- https://doi.org/10.1158/2643-3230.bcd-25-0278
- Primary Topic
- CAR-T cell therapy research
- Type
- article
- Field-Weighted Citation Impact
- 0.00