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| Item Type: | Article |
|---|---|
| Title: | Patient-tailored adoptive immunotherapy with EBV-specific T cells from related and unrelated donors |
| Creators: |
Bonifacius, A.  ORCID: https://orcid.org/0000-0002-0112-967X, Lamottke, B., Tischer-Zimmermann, S., Schultze-Florey, R., Goudeva, L., Heuft, H.G., Arseniev, L., Beier, R., Beutel, G. ORCID: https://orcid.org/0000-0001-6758-6104, Cario, G., Fröhlich, B., Greil, J. ORCID: https://orcid.org/0000-0003-1821-1183, Hansmann, L. ORCID: https://orcid.org/0000-0003-3790-0128, Hasenkamp, J., Höfs, M., Hundsdoerfer, P., Jost, E., Kafa, K., Kriege, O., Kröger, N. ORCID: https://orcid.org/0000-0001-5103-9966, Mathas, S. ORCID: https://orcid.org/0000-0001-9626-1413, Meisel, R. ORCID: https://orcid.org/0000-0001-5230-0628, Nathrath, M., Putkonen, M., Ravens, S., Reinhardt, H.C., Sala, E., Sauer, M.G, Schmitt, C. ORCID: https://orcid.org/0000-0002-4731-2226, Schroers, R. ORCID: https://orcid.org/0000-0003-2744-5491, Steckel, N.K., Trappe, R.U. ORCID: https://orcid.org/0000-0001-7565-7160, Verbeek, M., Wolff, D. ORCID: https://orcid.org/0000-0001-7015-3190, Blasczyk, R. ORCID: https://orcid.org/0000-0003-3875-3190, Eiz-Vesper, B. and Maecker-Kolhoff, B. ORCID: https://orcid.org/0000-0001-8164-514X
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| 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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