Patient-tailored adoptive immunotherapy with EBV-specific T cells from related and unrelated donors

Bonifacius, A.; Lamottke, B.; Tischer-Zimmermann, S.; Schultze-Florey, R.; Goudeva, L.; Heuft, H.G.; Arseniev, L.; Beier, R.; Beutel, G.; Cario, G.; Fröhlich, B.; Greil, J.; Hansmann, L.; Hasenkamp, J.; Höfs, M.; Hundsdoerfer, P.; Jost, E.; Kafa, K.; Kriege, O.; Kröger, N.; Mathas, S.; Meisel, R.; Nathrath, M.; Putkonen, M.; Ravens, S.; Reinhardt, H.C.; Sala, E.; Sauer, M.G; Schmitt, C.; Schroers, R.; Steckel, N.K.; Trappe, R.U.; Verbeek, M.; Wolff, D.; Blasczyk, R.; Eiz-Vesper, B.; Maecker-Kolhoff, B.

Patient-tailored adoptive immunotherapy with EBV-specific T cells from related and unrelated donors

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Item Type:	Article
Title:	Patient-tailored adoptive immunotherapy with EBV-specific T cells from related and unrelated donors
Creators Name:	Bonifacius, A., Lamottke, B., Tischer-Zimmermann, S., Schultze-Florey, R., Goudeva, L., Heuft, H.G., Arseniev, L., Beier, R., Beutel, G., Cario, G., Fröhlich, B., Greil, J., Hansmann, L., Hasenkamp, J., Höfs, M., Hundsdoerfer, P., Jost, E., Kafa, K., Kriege, O., Kröger, N., Mathas, S., Meisel, R., Nathrath, M., Putkonen, M., Ravens, S., Reinhardt, H.C., Sala, E., Sauer, M.G, Schmitt, C., Schroers, R., Steckel, N.K., Trappe, R.U., Verbeek, M., Wolff, D., Blasczyk, R., Eiz-Vesper, B. and Maecker-Kolhoff, B.
Abstract:	BACKGROUND: Adoptive transfer of EBV-specific T cells can restore specific immunity in immunocompromised patients with EBV-associated complications. METHODS: We provide results of a personalized T-cell manufacturing program evaluating donor, patient, T-cell product and outcome data. Patient-tailored clinical-grade EBV-specific cytotoxic T-lymphocyte (EBV-CTL) products from stem cell donors (SCD), related third party donors (TPD) or unrelated TPD from the allogeneic T-cell donor registry (alloCELL) established at Hannover Medical School were manufactured by immunomagnetic selection using CliniMACS Plus or Prodigy device and EBV PepTivators EBNA-1 and Select. Consecutive manufacturing processes were evaluated and patient outcome and side effects were retrieved by retrospective chart analysis. RESULTS: Forty clinical-grade EBV-CTL products from SCDs, related or unrelated TPDs were generated for 37 patients with and without transplantation (Tx) history within 5 days (median) after donor identification. 34 patients received 1-14 EBV-CTL products (fresh and cryopreserved). EBV-CTL transfer led to complete response in 20 of 29 patients who were evaluated for clinical response. No infusion-related toxicity was reported. EBV-specific T cells in patients' blood were detectable in 16/18 monitored patients (89 %) after transfer and correlated with clinical response. CONCLUSION: In conclusion, personalized clinical-grade manufacturing of EBV-CTL products via immunomagnetic selection from SCD, related or unrelated TPD is feasible in a timely manner. Overall, EBV-CTL were clinically effective and well-tolerated. Our data suggest EBV-CTL as promising therapeutic approach for immunocompromised patients with refractory EBV-associated diseases beyond HSCT as well as patients with pre-existing organ dysfunction.
Keywords:	Epstein-Barr Virus Infections, Human Herpesvirus 4, Adoptive Immunotherapy, Retrospective Studies, Cytotoxic T-Lymphocytes, Unrelated Donors
Source:	Journal of Clinical Investigation
ISSN:	0021-9738
Publisher:	American Society for Clinical Investigation
Volume:	133
Number:	12
Page Range:	e163548
Date:	15 June 2023
Official Publication:	https://doi.org/10.1172/JCI163548
PubMed:	View item in PubMed

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