Trials with second generation CD19 chimeric antigen receptors (CAR) T-cells report unprecedented responses but are associated with risk of cytokine release syndrome (CRS). Instead, we studied the use of donor Epstein–Barr virus-specific T-cells (EBV CTL) transduced with a first generation CD19CAR, relying on the endogenous T-cell receptor for proliferation. We conducted a multi-center phase I/II study of donor CD19CAR transduced EBV CTL in pediatric acute lymphoblastic leukaemia (ALL). Patients were eligible pre-emptively if they developed molecular relapse (>5 × 10-4) post first stem cell transplant (SCT), or prophylactically post second SCT. An initial cohort showed poor expansion/persistence. We therefore investigated EBV-directed vaccination to enhance expansion/persistence. Eleven patients were treated. No CRS, neurotoxicity or graft versus host disease (GVHD) was observed. At 1 month, 5 patients were in CR (4 continuing, 1 de novo), 1 PR, 3 had stable disease and 3 no response. At a median follow-up of 12 months, 10 of 11 have relapsed, 2 are alive with disease and 1 alive in CR 3 years. Although CD19CAR CTL expansion was poor, persistence was enhanced by vaccination. Median persistence was 0 (range: 0–28) days without vaccination compared to 56 (range: 0–221) days with vaccination (P=0.06). This study demonstrates the feasibility of multi-center studies of CAR T cell therapy and the potential for enhancing persistence with vaccination.Leukemia advance online publication, 10 March 2017; doi:10.1038/leu.2017.39
Rossig, C., Pule, M., Altvater, B., Saiagh, S., Wright, G., Ghorashian, S., et al. (2017). Vaccination to improve the persistence of CD19CAR gene-modified T cells in relapsed pediatric acute lymphoblastic leukemia. LEUKEMIA, 31(5), 1087-1095.
Citazione: | Rossig, C., Pule, M., Altvater, B., Saiagh, S., Wright, G., Ghorashian, S., et al. (2017). Vaccination to improve the persistence of CD19CAR gene-modified T cells in relapsed pediatric acute lymphoblastic leukemia. LEUKEMIA, 31(5), 1087-1095. |
Tipo: | Articolo in rivista - Articolo scientifico |
Carattere della pubblicazione: | Scientifica |
Presenza di un coautore afferente ad Istituzioni straniere: | Si |
Titolo: | Vaccination to improve the persistence of CD19CAR gene-modified T cells in relapsed pediatric acute lymphoblastic leukemia |
Autori: | Rossig, C; Pule, M; Altvater, B; Saiagh, S; Wright, G; Ghorashian, S; Clifton-Hadley, L; Champion, K; Sattar, Z; Popova, B; Hackshaw, A; Smith, P; Roberts, T; Biagi, E; Dreno, B; Rousseau, R; Kailayangiri, S; Ahlmann, M; Hough, R; Kremens, B; Sauer, M; Veys, P; Goulden, N; Cummins, M; Amrolia, P |
Autori: | |
Data di pubblicazione: | 2017 |
Lingua: | English |
Rivista: | LEUKEMIA |
Digital Object Identifier (DOI): | http://dx.doi.org/10.1038/leu.2017.39 |
Appare nelle tipologie: | 01 - Articolo su rivista |