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

Jeremy D. Rubinstein, Division of Oncology, Cincinnati Children's Hospital, Cincinnati, Ohio; Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio. Electronic address: Jeremy.rubinstein@cchmc.org.
Sonata Jodele, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio; Division of Bone Marrow Transplant and Immune Deficiency, Cincinnati Children's Hospital, Cincinnati, Ohio.
Daria Heyenbruch, Hoxworth Blood Center, Cincinnati, Ohio.
Jamie Wilhelm, Division of Bone Marrow Transplant and Immune Deficiency, Cincinnati Children's Hospital, Cincinnati, Ohio.
Shawn Thomas, Division of Bone Marrow Transplant and Immune Deficiency, Cincinnati Children's Hospital, Cincinnati, Ohio.
Carolyn Lutzko, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio; Experimental Hematology and Cancer biology, Cincinnati Children's Hospital, Cincinnati, Ohio.
Xiang Zhu, Experimental Hematology and Cancer biology, Cincinnati Children's Hospital, Cincinnati, Ohio.
Thomas Leemhuis, Hoxworth Blood Center, Cincinnati, Ohio.
Jose A. Cancelas, Hoxworth Blood Center, Cincinnati, Ohio; Experimental Hematology and Cancer biology, Cincinnati Children's Hospital, Cincinnati, Ohio.
Michael Keller, Program for Cell Enhancement and Technologies for Immunotherapy, Children's National Health System and The George Washington University, Washington, DC.
Catherine M. Bollard, Program for Cell Enhancement and Technologies for Immunotherapy, Children's National Health System and The George Washington University, Washington, DC.
Patrick J. Hanley, Program for Cell Enhancement and Technologies for Immunotherapy, Children's National Health System and The George Washington University, Washington, DC.
Zeinab El Boghdadly, Division of Infectious Diseases, The Ohio State University, Columbus, Ohio.
Alice Mims, Division of Hematology, The Ohio State University, Columbus, Ohio.
Stella M. Davies, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio; Division of Bone Marrow Transplant and Immune Deficiency, Cincinnati Children's Hospital, Cincinnati, Ohio.
Michael S. Grimley, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio; Division of Bone Marrow Transplant and Immune Deficiency, Cincinnati Children's Hospital, Cincinnati, Ohio.
Adam S. Nelson, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio; Division of Bone Marrow Transplant and Immune Deficiency, Cincinnati Children's Hospital, Cincinnati, Ohio.

Document Type

Journal Article

Publication Date

2-1-2022

Journal

Transplantation and cellular therapy

Volume

28

Issue

2

DOI

10.1016/j.jtct.2021.11.005

Keywords

Cellular therapy; JC virus; Progressive multifocal leukoencephalopathy; Stem cell transplantation; Virus-specific T cells

Abstract

Progressive multifocal leukoencephalopathy (PML) is a progressive and generally fatal demyelinating neurologic 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. To investigate treatment response and outcomes in recipients of hematopoietic stem cell transplantation (HSCT) with PML treated with third-party VSTs directed against the BK virus, a highly homologous polyoma virus that shares immunogenic epitopes with JCPyV. A retrospective chart review was performed on 4 patients who received VSTs for the treatment of PML at Cincinnati Children's Hospital Medical Center since 2019. VSTs were administered safely, with no cases of graft-versus-host disease and no infusion reactions. One patient who was treated almost immediately after diagnosis was able to clear JCPyV from blood and cerebrospinal fluid, with resultant stabilization of neurologic decline. IFN-γ enzyme-linked immunospot (ELISpot) analysis demonstrated VSTs 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, exhibited progressive neurologic decline despite varying degrees of improvement in viral load. 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 once PML is diagnosed. © 2021 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc.

Department

Pediatrics

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