Virus-specific T cells show promise in treating PML

In patients with progressive multifocal leukoencephalopathy (PML), a retrospective series of 28 patients showed that treatment with directly isolated allogeneic virus-specific (DIAVIS) T cells may reduce mortality and improve functional outcomes. These results provide the first class IV evidence for the treatment of this life-threatening infection.

Dr Lea Grote-Levi (Hannover Medical School, Germany) said that 2 innovative treatment options for PML are available: the immune checkpoint inhibitor pembrolizumab, and virus-specific T cells. A monocentric trial with DIAVIS T cells was recently conducted at the Hannover Medical School [1,2]. Between March 2020 and February 2022, 28 patients with PML received DIAVIS T cells as a single infusion with a maximum of 2x10⁴ CD3-positive cells/kg body weight per dose. These T cells were isolated from healthy donors, either related (n=9) or unrelated (n=19) to the patient, and were directed against the BK polyomavirus. Remaining T cells were cryopreserved and administered in additional doses approximately 2 and 6 weeks later. Of 28 patients treated with DIAVIS T cells, 17 had lymphoproliferative disorders, 5 had a systemic autoimmune disease, 4 had lymphopenia without prior immunotherapy, and 2 had aids.

The number of responders was 22 (79%). Their neurological symptoms stabilised or improved, and their viral load reduced. The 6 (21%) non-responders quickly deteriorated and died; during the 12-month follow-up period, another 2 patients died. The only factor that predicted poor treatment response was older age. Dr Grote-Levi added that 12-month survival rates were higher for DIAVIS-treated patients compared with historical controls receiving best supportive treatment: in the DIAVIS T cell group, 18 out of 26 patients survived after 1 year; in the historical control group, this was 57 out of 113 (HR 0.42; 95% CI 0.24–0.73; P=0.02).

Dr Grote-Levi and colleagues have a phase 2 trial in preparation, called CurePML (NCT06990087), to further evaluate this enriched anti-viral T-cell therapy.

1. Grote-Levi L. Directly isolated allogeneic virus-specific T cells in Progressive Multifocal Leukoencephalopathy. SPS05_1, EAN Congress 2025, 21-24 June 2025, Helsinki, Finland.
2. Möhn N, et al. JAMA Neurol. 2024;81(11):1187-98.

Medical writing support was provided by Michiel Tent.

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Posted on 24 June 20253 September 2025