Bonifacius, Agnes and Lamottke, Britta and Tischer-Zimmermann, Sabine and Schultze-Florey, Rebecca and Goudeva, Lilia and Heuft, Hans-Gert and Arseniev, Lubomir and Beier, Rita and Beutel, Gernot and Cario, Gunnar and Froehlich, Birgit and Greil, Johann and Hansmann, Leo and Hasenkamp, Justin and Hoefs, Michaela and Hundsdoerfer, Patrick and Jost, Edgar and Kafa, Kinan and Kriege, Oliver and Kroeger, Nicolaus and Mathas, Stephan and Meisel, Roland and Nathrath, Michaela and Putkonen, Mervi and Ravens, Sarina and Reinhardt, Hans Christian and Sala, Elisa and Sauer, Martin G. and Schmitt, Clemens and Schroers, Roland and Steckel, Nina Kristin and Trappe, Ralf Ulrich and Verbeek, Mareike and Wolff, Daniel and Blasczyk, Rainer and Eiz-Vesper, Britta and Maecker-Kolhoff, Britta (2023) Patient-tailored adoptive immunotherapy with EBV-specific T cells from related and unrelated donors. JOURNAL OF CLINICAL INVESTIGATION, 133 (12): e163548. ISSN 0021-9738, 1558-8238
Full text not available from this repository. (Request a copy)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 (SCDs), related third-party donors (TPDs), or unrelated TPDs from the allogeneic T cell donor registry (alloCELL) at Hannover Medical School were manufactured by immunomagnetic selection using a CliniMACS Plus or Prodigy device and the 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 TPDs, or unrelated TPDs were generated for 37 patients with refractory EBV infections or EBV-associated malignancies with and without a history of transplantation, within 5 days (median) after donor identification. Thirty-four patients received 1-14 EBV-CTL products (fresh and cryopreserved). EBV-CTL transfer led to a 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 of 18 monitored patients (89%) after transfer, and their presence correlated with clinical response.CONCLUSION. Personalized clinical-grade manufacture of EBV-CTL products via immunomagnetic selection from SCDs, related TPDs, or unrelated TPDs in a timely manner is feasible. Overall, EBV-CTLs were clinically effective and well tolerated. Our data suggest EBV-CTL transfer as a promising therapeutic approach for immunocompromised patients with refractory EBV-associated diseases beyond HSCT, as well as patients with preexisting organ dysfunction.TRIAL REGISTRATION. Not applicable.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | EPSTEIN-BARR-VIRUS; POSTTRANSPLANTATION LYMPHOPROLIFERATIVE DISEASE; RISK-FACTORS; RECIPIENTS; DISORDERS; INFECTIONS; IMMUNITY; THERAPY; PTLD; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin III (Hämatologie und Internistische Onkologie) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 30 Jan 2024 07:25 |
| Last Modified: | 30 Jan 2024 07:25 |
| URI: | https://pred.uni-regensburg.de/id/eprint/60955 |
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