Abstract
BackgroundProgressive multifocal leukoencephalopathy is a demyelinating CNS disorder. Reactivation of John Cunningham virus leads to oligodendrocyte infection with lysis and consequent axonal loss due to demyelination. Patients usually present with confusion and seizures. Late diagnosis and lack of adequate therapy options persistently result in permanent impairment of brain functions. Due to profound T cell depletion, impairment of T-cell function and potent immunosuppressive factors, allogeneic hematopoietic cell transplantation recipients are at high risk for JCV reactivation. To date, PML is almost universally fatal when occurring after allo-HCT.MethodsTo optimize therapy specificity, we enriched JCV specific T-cells out of the donor T-cell repertoire from the HLA-identical, anti-JCV-antibody positive family stem cell donor by unstimulated peripheral apheresis [1]. For this, we selected T cells responsive to five JCV peptide libraries via the Cytokine Capture System technology. It enables the enrichment of JCV specific T cells via identification of stimulus-induced interferon gamma secretion.ResultsDespite low frequencies of responsive T cells, we succeeded in generating a product containing 20 000 JCV reactive T cells ready for patient infusion. The adoptive cell transfer was performed without complication. Consequently, the clinical course stabilized and the patient slowly went into remission of PML with JCV negative CSF and containment of PML lesion expansion.ConclusionWe report for the first time feasibility of generating T cells with possible anti-JCV activity from a seropositive family donor, a variation of virus specific T-cell therapies suitable for the post allo transplant setting. We also present the unusual case for successful treatment of PML after allo-HCT via virus specific T-cell therapy.
Highlights
Progressive multifocal leukoencephalopathy is a demyelinating CNS disorder
The adoptive cell transfer of JC virus specific T cells was performed without complication roughly 2 months after Progressive multifocal leukoencephalopathy (PML) diagnosis
Our patient slowly went into remission of PML with JC virus negative Cerebrospinal fluid (CSF) 2.5 months after initial symptoms
Summary
Progressive multifocal leukoencephalopathy is a demyelinating CNS disorder. Reactivation of John Cunningham virus leads to oligodendrocyte infection with lysis and consequent axonal loss due to demyelination. Progressive multifocal leukoencephalopathy (PML) is a frequently fatal CNS disorder caused by reactivation of JC virus (JCV). BK virus and JCV are genetically related and share a number of immunogenic epitopes. Prior to that, another group had already generated JCV specific T cells from a HLA matched donor. The adoptive transfer of these cells was well tolerated and the patient showed neurological improvement [5]. These two cases argue to the potential of T-cell transfers after allo-HCT, only selected patients will be in a situation where T-cell transfer is an option
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.