A1 Vertaisarvioitu alkuperäisartikkeli tieteellisessä lehdessä
Patient-tailored adoptive immunotherapy with EBV-specific T cells from related and unrelated donors
Tekijät: Bonifacius A, Lamottke B, Tischer-Zimmermann S, Schultze-Florey R, Goudeva L, Heuft HG, Arseniev L, Beier R, Beutel G, Cario G, Frohlich B, Greil J, Hansmann L, Hasenkamp J, Hofs M, Hundsdoerfer P, Jost E, Kafa K, Kriege O, Kroger N, Mathas S, Meisel R, Nathrath M, Putkonen M, Ravens S, Reinhardt HC, Sala E, Sauer MG, Schmitt C, Schroers R, Steckel NK, Trappe RU, Verbeek M, Wolff D, Blasczyk R, Eiz-Vesper B, Maecker-Kolhoff B
Kustantaja: AMER SOC CLINICAL INVESTIGATION INC
Julkaisuvuosi: 2023
Lehti:: Journal of Clinical Investigation
Tietokannassa oleva lehden nimi: JOURNAL OF CLINICAL INVESTIGATION
Lehden akronyymi: J CLIN INVEST
Artikkelin numero: e163548
Vuosikerta: 133
Numero: 12
Sivujen määrä: 15
ISSN: 0021-9738
eISSN: 1558-8238
DOI: https://doi.org/10.1172/JCI163548
Verkko-osoite: https://www.jci.org/articles/view/163548
Rinnakkaistallenteen osoite: https://research.utu.fi/converis/portal/detail/Publication/180729241
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.
Ladattava julkaisu This is an electronic reprint of the original article. |