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Clinical-scale production of Aspergillus-specific T cells for the treatment of invasive aspergillosis in the immunocompromised host

Bone Marrow Transplantation volume 54, pages 1963–1972 (2019)Cite this article

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A Correction to this article was published on 20 June 2019

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Abstract

Invasive aspergillosis (IA) represents a leading cause of mortality in immunocompromised patients. Although adoptive immunotherapy with Aspergillus-specific T cells (Asp-STs) represents a promising therapeutic approach against IA, the complex and costly production limits its broader application. We generated Asp-STs from a single blood draw of healthy individuals or IA patients in only 10 days, by either Aspergillus fumigatus (AF) lysate or peptide stimulation of mononuclear cells. The cells were phenotypically and functionally characterized, and safety was assessed in xenografts. Healthy donor-derived and lysate- or peptide-pulsed Asp-STs presented comparable fold expansion, immunophenotype, and Th1 responses. Upon cross-stimulation, only the lysate-pulsed Asp-STs were empowered to respond to peptide stimulation, although both cell products induced hyphal damage. Importantly, Asp-STs cross-reacted with other fungal species and did not induce alloreactivity in vivo. IA patient-derived T cells displayed an anergic phenotype that prohibited sufficient expansion and yield of meaningful doses of Asp-STs for autologous immunotherapy. Using a rapid and simple process, we generated, from healthy donors but not IA patients, functionally active Asp-STs of broad specificity and at clinically relevant numbers. Such an approach may form the basis for the effective management of IA in the context of allogeneic hematopoietic cell transplantation.

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  • 20 June 2019

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Acknowledgements

This work was supported by the Greek State Scholarships Foundation, IKY fellowships of excellence for postdoctoral studies in Greece-SIEMENS program. Funding for this project was provided in part by an advanced EHA (European Hematology Association) Research Grant award and by a fellowship of excellence for postdoctoral studies from the Greek State Scholarships Foundation (IKY, SIEMENS program).

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Authors and Affiliations

  1. Hematology Department-Hematopoietic Cell Transplantation Unit, Gene and Cell Therapy Center, “George Papanikolaou” Hospital, Thessaloniki, 57010, Greece

    Anastasia Papadopoulou, Maria Alvanou, Kiriakos Koukoulias, Evangelia Athanasiou, Andriana Lazaridou, Nikolaos Savvopoulos, Achilles Anagnostopoulos & Evangelia Yannaki

  2. Department of Genetics, Development and Molecular Biology, School of Biology, Aristotle University of Thessaloniki, Thessaloniki, 54124, Greece

    Maria Alvanou, Kiriakos Koukoulias, Nikolaos Savvopoulos & Minas Yiangou

  3. Adult Hematology and Stem Cell Transplant, King Fahad Specialist Hospital Dammam, Dammam, 32253, Saudi Arabia

    Panayotis Kaloyannidis

  4. 1st Department of Microbiology, Medical School, Aristotle University of Thessaloniki, Thessaloniki, 54124, Greece

    Anthi-Marina Markantonatou & Timoleon-Achilleas Vyzantiadis

  5. Department of Medicine, University of Washington, Seattle, WA, 98195, USA

    Evangelia Yannaki

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  1. Anastasia Papadopoulou
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Papadopoulou, A., Alvanou, M., Koukoulias, K. et al. Clinical-scale production of Aspergillus-specific T cells for the treatment of invasive aspergillosis in the immunocompromised host. Bone Marrow Transplant 54, 1963–1972 (2019). https://doi.org/10.1038/s41409-019-0501-9

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