Off-the-Shelf Third-Party Virus-Specific T Cell Therapy to Treat JC Polyomavirus Infection in Hematopoietic Stem Cell Transplantation Recipients

Autor: Zeinab El Boghdadly, Xiang Zhu, Daria Heyenbruch, Stella M. Davies, Adam S. Nelson, Jamie Wilhelm, Sonata Jodele, Alice S. Mims, Carolyn Lutzko, Thomas Leemhuis, Shawn Thomas, Catherine M. Bollard, Michael D. Keller, Jeremy D. Rubinstein, Michael Grimley, Jose A. Cancelas, Patrick J. Hanley
Rok vydání: 2021
Předmět:
Zdroj: Transplantation and cellular therapy. 28(2)
ISSN: 2666-6367
Popis: Background Progressive multifocal leukoencephalopathy (PML) is a progressive and generally fatal demyelinating neurological disease that occurs in profoundly immunocompromised patients due to infection with the human polyomavirus JC virus (JCPyV). Treatment options are limited and are largely focused on restoring T-cell immunity and outcomes are historically poor. Control of JCPyV in the setting of an immunocompromised patient by adoptive transfer of third-party virus specific T-cells (VSTs) has been described in a small number of cases. Objective To investigate treatment response and outcomes in recipients of hematopoietic stem cell transplant (HSCT) with PML treated with third-party VSTs directed against BK virus, a highly homologous polyoma virus that shares immunogenic epitopes with JCPyV. Study Design Retrospective chart review was performed on four patients who received VSTs for the treatment of PML at Cincinnati Children's Hospital Medical Center since 2019 Results VSTs were safely administered with no cases of graft-vs-host disease and no infusion reactions. One patient, who was treated almost immediately after diagnosis, was able to clear JCPyV from blood and CSF with resultant stabilization of neurologic decline. Interferon-gamma ELISpot demonstrated virus specific T-cells in the peripheral blood following infusion. Response was maintained through repeat infusions. Three other patients, all of whom had a longer delay between diagnosis and infusion, had progressive neurologic decline despite varying degree of improvement in viral load. Conclusion PML is a rare but often fatal complication following HSCT for which few treatment options are available. BK directed, JCPyV cross-reactive VSTs are a safe and viable therapeutic option and prompt administration should be considered after a diagnosis of PML is made. Key points • Virus specific T cells targeting JCPyV virus are safe with no infusional toxicity or de-novo graft versus host disease. • Virus specific T-cells have evidence of efficacy in some cases of PML, but further studies are needed to determine factors that will optimize response.
Databáze: OpenAIRE
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