TY  - JOUR
A1  - Rossig, C
A1  - Pule, M
A1  - Altvater, B
A1  - Saiagh, S
A1  - Wright, G
A1  - Ghorashian, S
A1  - Clifton-Hadley, L
A1  - Champion, K
A1  - Sattar, Z
A1  - Popova, B
A1  - Hackshaw, A
A1  - Smith, P
A1  - Roberts, T
A1  - Biagi, E
A1  - Dreno, B
A1  - Rousseau, R
A1  - Kailayangiri, S
A1  - Ahlmann, M
A1  - Hough, R
A1  - Kremens, B
A1  - Sauer, MG
A1  - Veys, P
A1  - Goulden, N
A1  - Cummins, M
A1  - Amrolia, PJ
JF  - Leukemia
UR  - http://dx.doi.org/10.1038/leu.2017.39
SN  - 1476-5551
N2  - Trials with 2nd generation CD19 chimeric antigen receptors (CAR) T-cells report unprecedented responses but associated with risk of Cytokine Release Syndrome (CRS). Instead, we studied use of donor Epstein Barr virus-specific T-cells (EBV CTL) transduced with a 1st 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 ALL. Patients were eligible pre-emptively if they developed molecular relapse (>5 × 10-4) post-1st SCT, or prophylactically post-2nd SCT. An initial cohort showed poor expansion/persistence. We next investigated EBV-directed vaccination to enhance expansion/persistence. 11 patients were treated. No CRS, neurotoxicity or 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. Whilst 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 feasibility of such multi-center studies and the potential for enhancing persistence with vaccination.Leukemia accepted article preview online, 27 January 2017. doi:10.1038/leu.2017.39.
ID  - discovery1538549
N1  - © 2017 Macmillan Publishers Limited. All rights reserved.
VL  - 31
AV  - public
Y1  - 2017/03/10/
SP  - 1087
EP  - 1095
TI  - Vaccination to improve the persistence of CD19CAR gene-modified T cells in relapsed pediatric acute lymphoblastic leukemia
ER  -