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. 2024 Aug;26(4):e14296.
doi: 10.1111/tid.14296. Epub 2024 Jun 3.

Adenovirus- and cytomegalovirus-specific adoptive T-cell therapy in the context of hematologic cell transplant or HIV infection - A single-center experience

Benedikt Obermaier  1 , Christiane Braun  2 , Luca Hensen  1 , Osama Ahmad  1 , Christoph Faul  1 , Peter Lang  2 , Wolfgang Bethge  1 , Claudia Lengerke  1 , Wichard Vogel  1
Affiliations

Adenovirus- and cytomegalovirus-specific adoptive T-cell therapy in the context of hematologic cell transplant or HIV infection - A single-center experience

Benedikt Obermaier et al. Transpl Infect Dis. 2024 Aug.

Abstract

Background: Reactivation of viral infections, in particular cytomegalovirus (CMV) and adenovirus (ADV), cause morbidity and non-relapse-mortality in states of immune deficiency, especially after allogeneic hematopoietic cell transplantation (allo-HCT). Against the background of few available pharmacologic antiviral agents, limited by toxicities and resistance, adoptive transfer of virus-specific T-cells (VST) is a promising therapeutic approach.

Methods: We conducted a single-center retrospective analysis of adult patients treated with ADV- or CMV-specific T-cells in 2012-2022. Information was retrieved by review of electronic health records. Primary outcome was a response to VST by decreasing viral load or clinical improvement. Secondary outcomes included overall survival and safety of VST infusion, in particular association with graft-versus-host disease (GVHD).

Results: Ten patients were included, of whom four were treated for ADV, five for CMV, and one for ADV-CMV-coinfection. Cells were derived from stem cell donors (6/10) or third-party donors (4/10). Response criteria were met by six of 10 patients (4/4 ADV, 2/5 CMV, and 0/1 ADV-CMV). Overall survival was 40%. No infusion related adverse events were documented. Aggravation of GVHD after adoptive immunotherapy was observed in two cases, however in temporal association with a conventional donor lymphocyte infusion and a stem cell boost, respectively.

Conclusion: In this cohort, CMV- and ADV-specific T-cell therapy appear to be safe and effective. We describe the first reported case of virus-specific T-cell therapy for CMV reactivation not associated with transplantation but with advanced HIV infection. This encourages further evaluation of adoptive immunotherapy beyond the context of allo-HCT.

Keywords: adenovirus; adoptive immunotherapy; cytomegalovirus; virus‐specific T‐cells.

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References

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