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2014 ; 123
(24
): 3750-9
Nephropedia Template TP
gab.com Text
Twit Text FOAVip
Twit Text #
English Wikipedia
Closely related T-memory stem cells correlate with in vivo expansion of
CAR CD19-T cells and are preserved by IL-7 and IL-15
#MMPMID24782509
Xu Y
; Zhang M
; Ramos CA
; Durett A
; Liu E
; Dakhova O
; Liu H
; Creighton CJ
; Gee AP
; Heslop HE
; Rooney CM
; Savoldo B
; Dotti G
Blood
2014[Jun]; 123
(24
): 3750-9
PMID24782509
show ga
Adoptive transfer of T lymphocytes expressing a CD19-specific chimeric antigen
receptor (CAR.CD19) induces complete tumor regression in patients with lymphoid
malignancies. Although in vivo persistence of CAR-T cells correlates with
clinical responses, it remains unknown whether specific cell subsets within the
CAR-T-cell product correlate with their subsequent in vivo expansion and
persistence. We analyzed 14 patients with B-cell malignancies infused with
autologous CAR.CD19-redirected T cells expanded ex vivo using IL-2, and found
that their in vivo expansion only correlated with the frequency within the
infused product of a CD8(+)CD45RA(+)CCR7(+) subset, whose phenotype is closest to
"T-memory stem cells." Preclinical models showed that increasing the frequency of
CD8(+)CD45RA(+)CCR7(+) CAR-T cells in the infused line by culturing the cells
with IL-7 and IL-15 produced greater antitumor activity of CAR-T cells mediated
by increased resistance to cell death, following repetitive encounters with the
antigen, while preserving their migration to secondary lymphoid organs. This
trial was registered at www.clinicaltrials.gov as #NCT00586391 and #NCT00709033.