Allogeneic BK Virus-Specific T-Cell Treatment in 2 Patients With Progressive Multifocal Leukoencephalopathy

Abstract

ObjectiveProgressive 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.MethodsTwo 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.ResultsBoth 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.ConclusionsWe 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 EvidenceThis study provides Class IV evidence that for patients with PML, allogeneic transplant of BKV-CTL improved symptoms, reduced MRI changes, and decreased viral load.

Pathogen-specific T Cells: Targeting Old Enemies and New Invaders in Transplantation and Beyond

“… 244 As BKV and JC virus are closely related and share several immunogenic proteins, adoptive transfer of allogeneic JC-STs or BKV-STs has also been explored as treatment of PML. 49 , 65 , 76 – 78 , 86 Preliminary, albeit very promising, results of those trials demonstrated safety of the infusion of partially matched VSTs as well as alleviation of clinical symptoms, progressive decline of viral load in cerebrospinal fluid and an unprecedented survival beyond 1 year in a number of PML patients with poor expectation for survival. 49 , 65 , 76 – 78 , 86 …”

Zelltherapie in den Zeiten von SARS-CoV-2

“…Dies widerspricht den Berichten anderer Gruppen, deren Präparate sich von oben erwähnten dadurch unterscheiden, dass sie aus CD4+und CD8+Zellen bestehen, was bedeutsam sein könnte. Verträglichkeit und teilweise beeindruckende klinische Erfolge mit third-party Virusantigen-spezifischen T-Zellen werden berichtet 34 35 36 37 . Für die Wirkung adoptiver T-Zell-Präparate sind beim Empfänger eine Lymphopenie, Immunsuppression zum Zeitpunkt des Transfers, danach aber Freiheit von T-Zell-aktivitätssupprimierenden Medikamenten 38 Voraussetzung.…”

“…Dies widerspricht den Berichten anderer Gruppen, deren Präparate sich von oben erwähnten dadurch unterscheiden, dass sie aus CD4 + und CD8 + Zellen bestehen, was bedeutsam sein könnte. Verträglichkeit und teilweise beeindruckende klinische Erfolge mit thirdparty Virusantigen-spezifischen T-Zellen werden berichtet [34][35][36][37]. [39][40][41][42] oder an paramagnetischen Partikeln gekoppelter MHC-Peptid-Multimere [43,44], wobei sich wegen ihrer MHC-Unabhängigkeit erstere Methode klinisch stärker etabliert hat.…”

Advances in Treatment of Progressive Multifocal Leukoencephalopathy

“…Only one patient experienced mild IRIS, and none had transplantation‐related adverse events. 60 , 61 , 62 , 63 , 64 , 65 Thus, allogenic T‐cell transfer appears to be a promising therapeutic strategy in PML related to refractory immunosuppression. However, virus‐specific T‐cell allogenic transfer requires an infrastructure and a technical expertise that are available at only few centers.…”