Third-party virus-specific T cells for the treatment of double-stranded DNA viral reactivation and posttransplant lymphoproliferative disease after solid organ transplant

Ruby Khoury; Michael S Grimley; Adam S Nelson; Tom Leemhuis; Jose A Cancelas; Eleanor Cook; YunZu Wang; Daria Heyenbruch; Catherine M Bollard; Michael D Keller; Patrick J Hanley; Carolyn Lutzko; Giang Pham; Stella M Davies; Jeremy D Rubinstein

doi:10.1016/j.ajt.2024.04.009

Third-party virus-specific T cells for the treatment of double-stranded DNA viral reactivation and posttransplant lymphoproliferative disease after solid organ transplant

Am J Transplant. 2024 Apr 19:S1600-6135(24)00280-6. doi: 10.1016/j.ajt.2024.04.009. Online ahead of print.

Authors

Affiliations

¹ Division of Bone Marrow Transplant and Immune Deficiencies, Cancer and Blood Diseases Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA; Department of Pediatrics, University of Cincinnati, Cincinnati, Ohio, USA. Electronic address: ruby.khoury@cchmc.org.
² Division of Bone Marrow Transplant and Immune Deficiencies, Cancer and Blood Diseases Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA; Department of Pediatrics, University of Cincinnati, Cincinnati, Ohio, USA.
³ Hoxworth Blood Center, University of Cincinnati, Cincinnati, Ohio, USA.
⁴ Department of Pediatrics, University of Cincinnati, Cincinnati, Ohio, USA; Hoxworth Blood Center, University of Cincinnati, Cincinnati, Ohio, USA; Division of Experimental Hematology, Cancer and Blood Diseases Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.
⁵ Division of Bone Marrow Transplant and Immune Deficiencies, Cancer and Blood Diseases Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.
⁶ Department of Pediatrics, Center for Cancer and Immunology Research, Children's National Hospital, the George Washington University, Washington, District of Columbia, USA.
⁷ Department of Pediatrics, University of Cincinnati, Cincinnati, Ohio, USA; Division of Experimental Hematology, Cancer and Blood Diseases Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.
⁸ Division of Experimental Hematology, Cancer and Blood Diseases Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.
⁹ Department of Pediatrics, University of Cincinnati, Cincinnati, Ohio, USA; Division of Oncology, Cancer and Blood Diseases Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.

PMID: 38643944
DOI: 10.1016/j.ajt.2024.04.009

Abstract

Reactivation or primary infection with double-stranded DNA viruses is common in recipients of solid organ transplants (SOTs) and is associated with significant morbidity and mortality. Treatment with conventional antiviral medications is limited by toxicities, resistance, and a lack of effective options for adenovirus (ADV) and BK polyomavirus (BKPyV). Virus-specific T cells (VSTs) have been shown to be an effective treatment for infections with ADV, BKPyV, cytomegalovirus (CMV), and Epstein-Barr virus (EBV). Most of these studies have been conducted in stem cell recipients, and no large studies have been published in the SOT population to date. In this study, we report on the outcome of quadrivalent third-party VST infusions in 98 recipients of SOTs in the context of an open-label phase 2 trial. The 98 patients received a total of 181 infusions, with a median of 2 infusions per patient. The overall response rate was 45% for BKPyV, 65% for cytomegalovirus, 68% for ADV, and 61% for Epstein-Barr virus. Twenty percent of patients with posttransplant lymphoproliferative disorder had a complete response and 40% of patients had a partial response. All the VST infusions were well tolerated. We conclude that VSTs are safe and effective in the treatment of viral infections in SOT recipients.

Keywords: BK; CMV; EBV; PTLD; adenovirus; solid organ transplant; viral reactivation; virus-specific T cells.