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Muharrem Muftuoglu1, Amanda Olson1, David Marin1

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BK virus-specific T cells show promise in treating progressive multifocal leukoencephalopathy (PML). This therapy led to JC virus clearance or reduced viral load in immunosuppressed patients with PML.

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Area of Science:

  • Immunology
  • Virology
  • Neurology

Background:

  • Progressive multifocal leukoencephalopathy (PML) is a rare, often fatal, demyelinating disease caused by the JC virus.
  • JC virus and BK virus share genetic similarities, particularly in immunogenic proteins.
  • PML predominantly affects immunosuppressed individuals, necessitating novel therapeutic strategies.

Observation:

  • Three immunosuppressed patients diagnosed with PML were treated with ex vivo-expanded, third-party BK virus-specific T cells.
  • Patient immunosuppression causes included cord-blood transplantation conditioning, ruxolitinib treatment for myeloproliferative neoplasm, and acquired immunodeficiency syndrome.
  • Donor-derived T cells were detected in the cerebrospinal fluid (CSF) post-infusion.

Findings:

  • Two patients experienced clinical and imaging improvements, with JC virus clearance from CSF.
  • The third patient showed a reduced JC viral load and symptom stabilization until death 8 months post-treatment.
  • Two patients developed immune reconstitution syndrome, a known complication of T-cell therapies.

Implications:

  • BK virus-specific T cells represent a potential therapeutic option for PML.
  • This approach may offer a viable treatment for PML in various immunosuppressed populations.
  • Further research is warranted to optimize T-cell therapy for JC virus-associated diseases.