Selection of adenovirus-specific and Epstein-Barr virus-specific T cells with major histocompatibility class I streptamers under Good Manufacturing Practice (GMP)-compliant conditions

Freimueller C, Stemberger J, Artwohl M, Germeroth L, Witt V, Fischer G, Tischer S, Eiz-Vesper B, Knippertz I, Dörrie J, Schaft N, Lion T, Fritsch G, Geyeregger R (2015)

Publication Type: Journal article

Publication year: 2015

Journal

Cytotherapy Informa Healthcare

Book Volume: 17

Pages Range: 989-1007

Journal Issue: 7

DOI: 10.1016/j.jcyt.2015.03.613

Abstract

Despite antiviral drug therapies, human adenovirus (HAdV), cytomegalovirus (CMV) and Epstein-Barr virus (EBV) infections still contribute substantially to transplant-related death of patients after hematopoietic stem cell transplantation. Earlier clinical studies demonstrated successful adoptive transfer of magnetically selected CMV-specific T cells via removable, and thus Good Manufacturing Practice-compliant, major histocompatibility class I streptamers. Thus, the primary focus of the present study was the selection of HAdV-streptamer+ T cells, although in three experiments, EBV-streptamer+ T cells were also selected.Cells from leukaphereses of healthy donors were prepared in large (1-6 × 10(9)) and small (25 × 10(6)) cell batches. Whereas the larger batch was directly labeled with streptamers to select HAdV- and/or EBV-specific T cells (large-scale), the smaller batch was used to generate in vitro virus-specific T-cell lines before streptamer labeling for streptamer selection (small-scale). Isolation of HAdV- and/or EBV-specific T cells was performed with the use of the CliniMACS device.The purity of HAdV- and EBV-streptamer+ T cells among CD3+ cells, obtained from large-scale selection, was up to 6.7% and 44%, respectively. If HAdV- and EBV-streptamers were applied simultaneously, the purity of antigen-specific T cells reached up to 50.7%. A further increase in purity reaching up to 98% was achieved by small-scale selection of HAdV-specific T cells. All final products fulfilled the microbiological and chemical release criteria. Interferon-?-response indicating functional activity was seen in 6 of 9 HAdV and 2 of 3 EBV large-scale selections and in 2 of 3 HAdV small-scale selections.HAdV-streptamers were shown to be clinically feasible for few patients after the large-scale approach but for larger patient numbers if combined with EBV-streptamers or after the small-scale approach.

Authors with CRIS profile

Jan Dörrie Department of Dermatology Niels Schaft Department of Dermatology

Involved external institutions

Medizinische Universität Wien AT Austria (AT) St. Anna Kinderkrebsforschung AT Austria (AT) STAGE cell therapeutics GmbH DE Germany (DE) Medizinische Hochschule Hannover (MHH) / Hannover Medical School DE Germany (DE)

How to cite

APA:

Freimueller, C., Stemberger, J., Artwohl, M., Germeroth, L., Witt, V., Fischer, G.,... Geyeregger, R. (2015). Selection of adenovirus-specific and Epstein-Barr virus-specific T cells with major histocompatibility class I streptamers under Good Manufacturing Practice (GMP)-compliant conditions. Cytotherapy, 17(7), 989-1007. https://doi.org/10.1016/j.jcyt.2015.03.613

MLA:

Freimueller, Christine, et al. "Selection of adenovirus-specific and Epstein-Barr virus-specific T cells with major histocompatibility class I streptamers under Good Manufacturing Practice (GMP)-compliant conditions." Cytotherapy 17.7 (2015): 989-1007.

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