TY - JOUR
T1 - Allogeneic BK virus-specific t cells for progressive multifocal leukoencephalopathy
AU - Muftuoglu, Muharrem
AU - Olson, Amanda
AU - Marin, David
AU - Ahmed, Sairah
AU - Mulanovich, Victor
AU - Tummala, Sudhakar
AU - Chi, T. Linda
AU - Ferrajoli, Alessandra
AU - Kaur, Indreshpal
AU - Li, Li
AU - Champlin, Richard
AU - Shpall, Elizabeth J.
AU - Rezvani, Katayoun
N1 - Funding Information:
Supported in part by an M.D. Anderson Cancer Center AML Moonshot Grant. The flow studies were supported by a grant from the National Institutes of Health (5R01CA061508-21) to Drs. Rezvani and Shpall and were performed in the Flow Cytometry and Cellular Imaging Facility, which is supported in part by the National Institutes of Health through a support grant to M.D. Anderson Cancer Center (CA016672).
Publisher Copyright:
© 2018 Massachusetts Medical Society.
PY - 2018/10/11
Y1 - 2018/10/11
N2 - 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 cerebrospinal 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. Donorderived T cells were detected in the CSF after infusion. (Funded by the M.D. Anderson Cancer Center Moon Shots Program and the National Institutes of Health; ClinicalTrials.gov number, NCT02479698.).
AB - 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 cerebrospinal 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. Donorderived T cells were detected in the CSF after infusion. (Funded by the M.D. Anderson Cancer Center Moon Shots Program and the National Institutes of Health; ClinicalTrials.gov number, NCT02479698.).
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U2 - 10.1056/NEJMoa1801540
DO - 10.1056/NEJMoa1801540
M3 - Article
C2 - 30304652
AN - SCOPUS:85054774011
SN - 0028-4793
VL - 379
SP - 1443
EP - 1451
JO - New England Journal of Medicine
JF - New England Journal of Medicine
IS - 15
ER -