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Updated: Nov 5, 2025
Generation of Multivirus-specific T Cells to Prevent/treat Viral Infections after Allogeneic Hematopoietic Stem Cell Transplant
Published on: May 27, 2011
Allogeneic BK Virus-Specific T-Cell Treatment in 2 Patients With Progressive Multifocal Leukoencephalopathy
Franziska Hopfner1, Nora Möhn2, Britta Eiz-Vesper2
1From the Department of Neurology (F.H., N. Möhn, M.S., G.H., T.S.), Hannover Medical School; Institute of Transfusion Medicine and Transplant Engineering (B.E.-V., R.B.), Hannover Medical School; Department of Pediatric Hematology and Oncology (B.M.-K.), Hannover Medical School; Hannover Medical School (B.M.-K.), Institute for Transfusion Medicine; Department of Respiratory Medicine (J.G.), Hannover Medical School; Department of Diagnostic and Interventional Neuroradiology (N. Mahmoudi, M.P.W.), Hannover Medical School, Hannover; Department of Neurology (N. Mahmoudi, K.P., M.P.W.), Carl Von Ossietzky University, Oldenburg; and Institute of Virology (O.A.), Medical Faculty, Heinrich-Heine University Düsseldorf, Germany. Hopfner.Franziska@mh-hannover.de.
Objective:
Progressive multifocal leukoencephalopathy (PML) is a devastating demyelinating opportunistic infection of the brain caused by the ubiquitously distributed JC polyomavirus. There are no established treatment options to stop or slow down disease progression. In 2018, a case series of 3 patients suggested the efficacy of allogeneic BK virus-specific T-cell (BKV-CTL) transplantation.
Methods:
Two patients, a bilaterally lung transplanted patient on continuous immunosuppressive medication since 17 years and a patient with dermatomyositis treated with glucocorticosteroids, developed definite PML according to AAN diagnostic criteria. We transplanted both patients with allogeneic BKV-CTL from partially human leukocyte antigen (HLA) compatible donors. Donor T cells had directly been produced from leukapheresis by the CliniMACS IFN-γ cytokine capture system. In contrast to the previous series, we identified suitable donors by HLA typing in a preexamined registry and administered 1 log level less cells.
Results:
Both patients' symptoms improved significantly within weeks. During the follow-up, a decrease in viral load in the CSF and a regression of the brain MRI changes occurred. The transfer seemed to induce endogenous BK and JC virus-specific T cells in the host.
Conclusions:
We demonstrate that this optimized allogeneic BKV-CTL treatment paradigm represents a promising, innovative therapeutic option for PML and should be investigated in larger, controlled clinical trials.
Classification Of Evidence:
This study provides Class IV evidence that for patients with PML, allogeneic transplant of BKV-CTL improved symptoms, reduced MRI changes, and decreased viral load.
Insights
Allogeneic BK virus-specific T-cell (BKV-CTL) transplantation offers a promising treatment for progressive multifocal leukoencephalopathy (PML). This innovative therapy improved patient symptoms, reduced viral load, and decreased brain MRI changes.
Area of Science:
- Neuroimmunology
- Viral Infections
- Cellular Therapy
Background:
- Progressive multifocal leukoencephalopathy (PML) is a severe demyelinating brain infection caused by the JC polyomavirus.
- Currently, no effective treatments exist to halt or reverse PML progression.
- Previous case series suggested potential efficacy of allogeneic BK virus-specific T-cell (BKV-CTL) transplantation.
Observation:
- Two patients with definite PML, one post-lung transplant and another with dermatomyositis, received allogeneic BKV-CTL therapy.
- Donors were identified via HLA typing, and T-cells were generated using the CliniMACS IFN-γ cytokine capture system.
- A reduced cell dose was administered compared to previous studies.
Findings:
- Both patients experienced significant symptom improvement within weeks of BKV-CTL transplantation.
- Cerebrospinal fluid (CSF) viral load decreased, and brain MRI showed regression of demyelinating lesions.
- The allogeneic BKV-CTL transfer appeared to stimulate the host's endogenous antiviral T-cell response.
Implications:
- Optimized allogeneic BKV-CTL transplantation presents a novel and promising therapeutic strategy for PML.
- This approach warrants further investigation in larger, controlled clinical trials to confirm efficacy and safety.
- The findings suggest a potential new avenue for managing opportunistic infections in immunocompromised individuals.
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