CELL INTELLIGENCE · 肿瘤细胞治疗研究

Background : B-cell malignancies have been effectively treated using chimeric antigen receptor-T (CAR-T) treatment employing traditional T cells. However, because of several obstacles, application in acute myeloid leukemia (AML) is still restricted. A safer "off-the-shelf" alternative can be supplied by CAR- T cells, which have major histocompatibility complex (MHC)-independent tumor identification capabilities and a decreased risk of graft versus host disease (GvHD). This study aimed to develop FLT3-targeted CAR- T cells that co-express cytokines (IL-2 or IL-7) to increase their anti-AML persistence and therapeutic efficacy. Methods : FLT3-CAR- T cells, FLT3-IL2-CAR- T cells, and FLT3-IL7-CAR- T cells were constructed. Their antitumor potency was comprehensively assessed through cytotoxicity assays, cytokine release, and persistence evaluation in vitro (using AML cell lines and primary AML cells) and in vivo (via mouse model). Results : Superior cytotoxicity against AML cell lines (OCI-AML3, MOLM-13, THP-1, and MV4-11) was demonstrated by FLT3-IL2-CAR- T cells, which also released higher levels of granzyme B, interferon- (IFN- ), and tumor necrosis factor- (TNF- ). FLT3-IL2-CAR- T cells exhibited cytotoxicity in some primary AML cells in vitro. During the antigen-repeated stimulation assay, FLT3-IL2-CAR- T cells preserved the stem cell-like memory T (T SCM ) cell subsets, sustained cytokine release, and maintained excellent viability. FLT3-IL2-CAR- T cells considerably slowed the development of AML in vivo and extended the existence (>68 days) of mice. Conclusions : FLT3-IL2-CAR- T cells exhibit potent and durable anti-AML activity, providing a novel strategy for clinical AML immunotherapy.