Virus-specific T-cell therapy to treat BK polyomavirus infection in bone marrow and solid organ transplant recipients

Abstract

BK polyomavirus (BKPyV) infection is a major complication of hematopoietic stem cell transplant (HSCT) and solid organ transplant (SOT). Treatment options are limited, poorly effective, and have significant toxicities. Cellular therapy using T cells directed against BKPyV is an emerging therapy, and we report efficacy in controlling BKPyV-associated disease in highly immunocompromised patients. Virus-specific T cells (VSTs) against BKPyV were manufactured using either blood from the patient's stem cell donor (donor-derived VSTs) or from unrelated donors (third-party VSTs). VSTs were used to treat BKPyV in 38 HSCT recipients and 3 SOT recipients between June 2017 and December 2019. Overall response rate was 86% in patients treated for BK viremia, 100% in patients treated for hemorrhagic cystitis, and 87% in patients treated for both BK viremia and hemorrhagic cystitis. No infusional toxicity, de novo graft-versus-host disease, or rejection of the organ occurred attributable to the VST infusion. BKPyV-specific immune responses were demonstrated by interferon-γ production by peripheral blood mononuclear cells postinfusion in response to BKPyV antigens. VSTs are a safe and potentially effective strategy to treat BKPyV and associated symptoms in recipients of HSCT and SOT. Cellular therapy should be considered for all patients with BKPyV and underlying immune suppression at risk of complications. This trial was registered at www.clinicaltrials.gov as #NCT02532452.

Conflict of interest statement

Conflict-of-interest disclosure: C.M.B. is on the advisory board for Cellectis and is on the scientific advisory boards for Catamaran Bio and Mana Therapeutics with stock and/or ownership, is on the board of directors for Caballeta Bio with stock options, and has stock in Neximmune and Torque Therapeutics. P.J.H. is a cofounder and on the board of directors of Mana Therapeutics and has filed intellectual property related to virus-specific T cells. S.M.D. has a US pending patent application under review, received research support from Alexion Pharmaceuticals, and consultancy from Novartis. S.J. has a US pending patent application under review and received travel support and consultancy fees from Omeros (unrelated to this work). The remaining authors declare no competing financial interests.

© 2020 by The American Society of Hematology.

Figures

Graphical abstract

Figure 1.

Response to VSTs. (A) Response to donor-derived BKPyV-VST flowchart. (B) Response to third-party BK-VST flowchart.

Figure 2.

Characteristics of the cellular and viral response. (A) The median number of BKPyV-specific T cells pre- and post-VST infusion. Interferon-γ response and corresponding viral PCR in patients who require 1 VST infusion (B), in a patient requiring multiple VST infusions (C), and in 1 patient who did not respond to VST infusion (D).