Treatment of acute lymphoblastic leukaemia with the second generation of CD19 CAR-T containing either CD28 or 4-1BB.

Abstract:

:T cells modified with anti-CD19 chimeric antigen receptor (CAR) containing either CD28 or 4-1BB (also termed TNFRSF9, CD137) costimulatory signalling have shown great potential in the treatment of acute lymphoblastic leukaemia (ALL). However, the difference between CD28 and 4-1BB costimulatory signalling in CAR-T treatment has not been well elucidated in clinical trials. In this study, we treated 10 relapsed or refractory ALL patients with the second generation CD19 CAR-T. The first 5 patients were treated with CD28-CAR and the other 5 patients were treated with 4-1BB CAR-T. All the 10 patients were response-evaluable. Three patients achieved complete remission and 1 patient with extramedullary disease achieved partial response after CD28-CAR-T treatment. In the 4-1BB CAR-T treatment group, 3 patients achieved complete remission. Furthermore, FLT-3 ligand (FLT3LG) was highly correlated with response time and may serve as a prognosis factor. No severe adverse events were observed in these 10 treated patients. Our study showed that both CD28 CAR-T and 4-1BB CAR-T both worked for response but they differed in response pattern (peak reaction time, reaction lasting time and reaction degree), adverse events, cytokine secretion and immune-suppressive factor level.

journal_name

Br J Haematol

authors

Li S,Zhang J,Wang M,Fu G,Li Y,Pei L,Xiong Z,Qin D,Zhang R,Tian X,Wei Z,Chen R,Chen X,Wan J,Chen J,Wei X,Xu Y,Zhang P,Wang P,Peng X,Yang S,Shen J,Yang Z,Chen J,Qian C

doi

10.1111/bjh.15195

subject

Has Abstract

pub_date

2018-05-01 00:00:00

pages

360-371

issue

3

eissn

0007-1048

issn

1365-2141

journal_volume

181

pub_type

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