Rapamycin Pretreatment Rescues the Bone Marrow AML Cell Elimination Capacity of CAR-T Cells.

ABSTRACT:

Purpose

Ongoing clinical trials show limited efficacy for Chimeric antigen receptor (CAR) T treatment for acute myeloid leukemia (AML). The aim of this study was to identify potential causes of the reported limited efficacy from CAR-T therapies against AML.

Experimental design

We generated CAR-T cells targeting Epithelial cell adhesion molecule (EpCAM) and evaluated their killing activity against AML cells. We examined the impacts of modulating mTORC1 and mTORC2 signaling in CAR-T cells in terms of CXCR4 levels. We examined the effects of a rapamycin pretreatment of EpCAM CAR-T cells (during ex vivo expansion) and assessed the in vivo antitumor efficacy of rapamycin-pretreated EpCAM CAR-T cells (including CXCR4 knockdown cells) and CD33 CAR-T cells in le

SUBMITTER: Nian Z 

PROVIDER: S-EPMC9401534 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature