BACKGROUND. Chimeric antigen receptor (CAR) T cell immunotherapy has resulted in complete remission (CR) and durable response in highly refractory patients. However, logistical complexity and high costs of manufacturing autologous viral products limit CAR T cell availability. METHODS. We report the early results of a phase I/II trial in B cell acute lymphoblastic leukemia (B-ALL) patients relapsed after allogeneic hematopoietic stem cell transplantation (HSCT) using donor-derived CD19 CAR T cells generated with the Sleeping Beauty (SB) transposon and differentiated into cytokine-induced killer (CIK) cells. RESULTS. The cellular product was produced successfully for all patients from the donor peripheral blood (PB) and consisted mostly of CD3+ lymphocytes with 43% CAR expression. Four pediatric and 9 adult patients were infused with a single dose of CAR T cells. Toxicities reported were 2 grade I and 1 grade II cytokine-release syndrome (CRS) cases at the highest dose in the absence of graft-versus-host disease (GVHD), neurotoxicity, or dose-limiting toxicities. Six out of 7 patients receiving the highest doses achieved CR and CR with incomplete blood count recovery (CRi) at day 28. Five out of 6 patients in CR were also minimal residual disease negative (MRD–). Robust expansion was achieved in the majority of the patients. CAR T cells were measurable by transgene copy PCR up to 10 months. Integration site analysis showed a positive safety profile and highly polyclonal repertoire in vitro and at early time points after infusion. CONCLUSION. SB-engineered CAR T cells expand and persist in pediatric and adult B-ALL patients relapsed after HSCT. Antileukemic activity was achieved without severe toxicities.
Magnani, C., Gaipa, G., Lussana, F., Belotti, D., Gritti, G., Napolitano, S., et al. (2020). Sleeping Beauty-engineered CAR T cells achieve anti-leukemic activity without severe toxicities. THE JOURNAL OF CLINICAL INVESTIGATION, 130(11), 6021-6033 [10.1172/JCI138473].
|Citazione:||Magnani, C., Gaipa, G., Lussana, F., Belotti, D., Gritti, G., Napolitano, S., et al. (2020). Sleeping Beauty-engineered CAR T cells achieve anti-leukemic activity without severe toxicities. THE JOURNAL OF CLINICAL INVESTIGATION, 130(11), 6021-6033 [10.1172/JCI138473].|
|Tipo:||Articolo in rivista - Articolo scientifico|
|Carattere della pubblicazione:||Scientifica|
|Presenza di un coautore afferente ad Istituzioni straniere:||No|
|Titolo:||Sleeping Beauty-engineered CAR T cells achieve anti-leukemic activity without severe toxicities|
|Autori:||Magnani, C; Gaipa, G; Lussana, F; Belotti, D; Gritti, G; Napolitano, S; Matera, G; Cabiati, B; Buracchi, C; Borleri, G; Fazio, G; Zaninelli, S; Tettamanti, S; Cesana, S; Colombo, V; Quaroni, M; Cazzaniga, G; Rovelli, A; Biagi, E; Galimberti, S; Calabria, A; Benedicenti, F; Montini, E; Ferrari, S; Introna, M; Balduzzi, A; Valsecchi, M; Dastoli, G; Rambaldi, A; Biondi, A|
MAGNANI, CHIARA FRANCESCA (Primo)
Gaipa, Giuseppe (Secondo)
BIONDI, ANDREA (Ultimo) (Corresponding)
|Data di pubblicazione:||2020|
|Rivista:||THE JOURNAL OF CLINICAL INVESTIGATION|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1172/JCI138473|
|Appare nelle tipologie:||01 - Articolo su rivista|