Treatment of Progressive Multifocal Leukoencephalopathy With Third-Party Allogeneic BK Virus T Cells
Abstract
Background: Progressive multifocal leukoencephalopathy (PML) is a fatal demyelinating disease caused by JC polyomavirus that affects immunosuppressed individuals and has no approved therapy. Here, we evaluate the safety and efficacy of third-party, off-the-shelf, partially HLA-matched BK virus-specific T cells (BK-VST) in patients with PML.
Methods: We conducted a single-center phase 2 study (including 3 patients treated under compassionate or emergency, INDs); 37 patients received most closely HLA-matched BK-VST at a median dose of 2.0 × 105 T cells/kg, with additional infusions permitted for subjects who did not achieve a complete response (CR). Twenty-three patients had an underlying diagnosis of hematologic malignancy. Each patient received a median of 2 doses (range, 1–12; IQR 2). Overall response (OR) was defined as virologic response with neurologic stabilization or improvement.
Results: During 12 months of follow-up, 21 patients (56.8%) achieved an OR, including 16 (43.2%) with a CR or CR with neurologic sequelae (CRnesq). Responses were rapid (median 23 days) and durable, with no loss of response observed despite limited HLA matching. The 1-year overall survival was 61.1% (95% CI, 41.9–77.4). Patients achieving an OR after the first infusion had markedly improved 1-year survival compared with nonresponders (93.3% vs 0%; P < .001). Greater HLA matching correlated with clinical benefit.
Conclusions: These data demonstrate that third-party BK-VST infusions are safe and potentially effective, supporting a scalable immunotherapeutic approach for this otherwise fatal disease.
Clinical Trials Registration. NCT02479698.
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BibTeX
@article{olson2026treatment,
title = {{Treatment of Progressive Multifocal Leukoencephalopathy With Third-Party Allogeneic BK Virus T Cells}},
author = {Amanda Olson and Ye Li and David Marin and Peter F Thall and Roland L Bassett and Melissa Barnett and Rafet Basar and Pinaki P Banerjee and T Anne Kleiman and Merry Chen and Jennie Rexer and Max Wintermark and Jeanie Choi and Kim Learned and Indreshpal Kaur and Melihate Sylejmani and Glorette Abueg and Roy F Chemaly and Victor Mulanovich and Rejeena Shrestha and Nadima Uprety and Karla M Castro and May Daher and Isabel M Galvan and Dominique Washington and Richard E Champlin and Elizabeth J Shpall and Katayoun Rezvani},
journal = {Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America},
year = {2026},
month = jul,
doi = {10.1093/cid/ciag404},
url = {https://doi.org/10.1093/cid/ciag404},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Treatment of Progressive Multifocal Leukoencephalopathy With Third-Party Allogeneic BK Virus T Cells
AU - Amanda Olson
AU - Ye Li
AU - David Marin
AU - Peter F Thall
AU - Roland L Bassett
AU - Melissa Barnett
AU - Rafet Basar
AU - Pinaki P Banerjee
AU - T Anne Kleiman
AU - Merry Chen
AU - Jennie Rexer
AU - Max Wintermark
AU - Jeanie Choi
AU - Kim Learned
AU - Indreshpal Kaur
AU - Melihate Sylejmani
AU - Glorette Abueg
AU - Roy F Chemaly
AU - Victor Mulanovich
AU - Rejeena Shrestha
AU - Nadima Uprety
AU - Karla M Castro
AU - May Daher
AU - Isabel M Galvan
AU - Dominique Washington
AU - Richard E Champlin
AU - Elizabeth J Shpall
AU - Katayoun Rezvani
PY - 2026
DA - 2026/07/06
JO - Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
DO - 10.1093/cid/ciag404
UR - https://doi.org/10.1093/cid/ciag404
AB - Background: Progressive multifocal leukoencephalopathy (PML) is a fatal demyelinating disease caused by JC polyomavirus that affects immunosuppressed individuals and has no approved therapy. Here, we evaluate the safety and efficacy of third-party, off-the-shelf, partially HLA-matched BK virus-specific T cells (BK-VST) in patients with PML. Methods: We conducted a single-center phase 2 study (including 3 patients treated under compassionate or emergency, INDs); 37 patients received most closely HLA-matched BK-VST at a median dose of 2.0 × 105 T cells/kg, with additional infusions permitted for subjects who did not achieve a complete response (CR). Twenty-three patients had an underlying diagnosis of hematologic malignancy. Each patient received a median of 2 doses (range, 1–12; IQR 2). Overall response (OR) was defined as virologic response with neurologic stabilization or improvement. Results: During 12 months of follow-up, 21 patients (56.8%) achieved an OR, including 16 (43.2%) with a CR or CR with neurologic sequelae (CRnesq). Responses were rapid (median 23 days) and durable, with no loss of response observed despite limited HLA matching. The 1-year overall survival was 61.1% (95% CI, 41.9–77.4). Patients achieving an OR after the first infusion had markedly improved 1-year survival compared with nonresponders (93.3% vs 0%; P < .001). Greater HLA matching correlated with clinical benefit. Conclusions: These data demonstrate that third-party BK-VST infusions are safe and potentially effective, supporting a scalable immunotherapeutic approach for this otherwise fatal disease. Clinical Trials Registration. NCT02479698.
SN - 1058-4838
SN - 1537-6591
ER -