Successful BK virus-specific T cell therapy in a kidney transplant recipient with progressive multifocal leukoencephalopathy

The strategy for progressive multifocal leukoencephalopathy (PML) in solid organ transplant recipients primarily focuses on reducing immunosuppressive therapy. However, this approach offers limited efficacy and carries a high risk of graft loss. Here, we present the case of a 64-year-old male kidney transplant recipient with a high degree of immunosuppression who developed PML in October 2022. Despite the standard reduction of immunosuppressive therapy, the patient's condition continued to deteriorate, as evidenced by worsening neurological symptoms and increasing JC virus (JCV) DNA levels in cerebrospinal fluid. This prompted the innovative use of BKPyV-virus-specific T cell (BKPyV-VST) therapy, given the genetic similarities between BK and JCVs. Infusion of third-party donor BKPyV-VST resulted in clinical stabilization, a significant reduction in JCVDNA levels, and the emergence of a JCV-specific T cell response, as observed in enzymelinked immunospot assays and TCR beta sequencing. This represents the first case report of successful third-party BKPyV-VST therapy in a kidney recipient presenting PML, without graft-versus-host disease or graft dysfunction.