Allogeneic BK Virus–Specific T Cells for Progressive Multifocal Leukoencephalopathy

Abstract

T h e ne w e ngl a nd jou r na l o f m e dicine n engl j med 379;15 nejm.org October 11, 2018 1443 Brief Report Summ a r y JC virus, the cause of progressive multifocal leukoencephalopathy (PML), and the BK virus are genetically similar and share sequence homology in immunogenic proteins. We treated three immunosuppressed patients with PML with ex vivo-expanded, partially HLA-matched, third-party-produced, cryopreserved BK virus-specific T cells. The immunosuppression in these patients was due to the conditioning regimen for cord-blood transplantation in one patient, a myeloproliferative neoplasm treated with ruxolitinib in another, and acquired immunodeficiency syndrome in the third. After T-cell infusion in two of the patients, alleviation of the clinical signs and imaging features of PML was seen and JC virus in the cere-brospinal fluid (CSF) cleared. The other patient had a reduction in JC viral load and stabilization of symptoms that persisted until her death 8 months after the first infusion. Two of the patients had immune reconstitution syndrome. Donor-derived T cells were detected in the CSF after infusion. (Funded by the M.D. Ander-son Cancer Center Moon Shots Program and the National Institutes of Health; ClinicalTrials.gov number, NCT02479698.) P rogressive multifocal leukoencephalopathy (PML) is a rare de-myelinating infection of the central nervous system caused by reactivation of the JC polyomavirus 1,2 that occurs in the context of defective cellular immunity. 3 Common underlying conditions that are associated with JC virus infection include advanced human immunodeficiency virus (HIV) infection, hematologic and solid-tissue cancers, hematopoietic stem-cell transplantation, and the use of certain immunosuppressive drugs, including biologic therapies such as natalizu-mab. 4-7 The infection typically causes altered mental status, motor deficits, ataxia, and visual symptoms and is progressive and usually fatal. There is no effective treatment for PML other than the restoration of cellular immune function, which is not feasible for many patients. 8 Several approaches for the treatment of PML, including the use of antiviral medications and mirtazapine, have been tested, with poor results. 8 Both JC virus and BK virus (named after patients in whom they were detected) belong to the Polyomaviridae family. 9 BK virus causes nephritis and cystitis in patients who have undergone stem-cell transplantation and in recipients of transplanted solid organs. Several groups, including ours, have successfully used viral-specific From the Departments of Stem Cell Trans-plantation and Cellular Therapy (M.M.,