.png){kind=icon}
.png){kind=icon}
Return
TIM3-targeted delivery of venetoclax overcomes drug resistance and reinvigorates NK cell activity in acute myeloid leukemia
.png){kind=icon}
PRE
AI
王
J
X
L
H
Y
R
C
Y
Y
Y
J
Y
W
Y
S
X
H
S
P
DOI：10.1038/s43018-026-01217-z.png)
.png){kind=icon}
Original request for help.png){kind=icon}
Share.png){kind=icon}
Save
Abstract
En 中文
Acute myeloid leukemia (AML) remains challenging, especially for older or unfit individuals who develop resistance to venetoclax (VEN)-based regimens. Although TIM3 represents a promising AML target, clinical blockade has yielded suboptimal outcomes. Here, we develop VINCENT (VEN-integrated natural killer cell engager targeting TIM3), a therapeutic platform combining anti-CD16 and anti-TIM3 antibodies with nanoformulated VEN. In VEN-resistant AML cell lines and patient-derived xenograft models, VINCENT overcomes resistance by enhancing VEN delivery, eliminating TIM3+ blasts and dysfunctional T cells and activating natural killer (NK) cells. In primary AML samples, VINCENT selectively kills drug-resistant blasts, with efficacy correlating with the NK cell-to-TIM3+ blast ratio. Single-cell transcriptomics reveals VINCENT depletes high-TIM3 blasts and remodels the immunosuppressive microenvironment toward immune competence. Collectively, VINCENT simultaneously addresses VEN resistance, NK cell dysfunction and immune evasion, offering a personalized option for elderly or unfit individuals with AML failing standard VEN regimens. Qian and colleagues report the characterization of venetoclax-loaded nanoparticles conjugated with anti-CD16 and anti-TIM3 antibodies, showing that the platform overcomes venetoclax resistance and reinvigorates natural killer cell activity in acute myeloid leukemia.
Journal
IF:
28.5
Papers:
1.2K
Citations:
1.1W
View more organizations