title: Fusion of dendritic cells and CD34+CD38- acute myeloid leukemia (AML) cells potentiates targeting AML-initiating cells by specific CTL induction.
abstract: Distinct leukemia-initiating cells (L-ICs) represent a critical target for therapeutic intervention of acute myeloid leukemia (AML). A potential strategy to eradicate L-ICs is to generate L-IC-specific cytotoxic T lymphocytes (CTLs). However, owing to rarity and immortality of L-ICs, it is difficult for antigen-presenting cells to capture L-ICs for specific antigen presentation. Here, we report a novel approach by fusing allogeneic dendritic cells (DCs) and CD34CD38 AML progenitor cells, through which specific CTLs were effectively induced, leading to the cytolysis to AML-initiating cells. Fusion of either DC/CD34CD38 AML cell or DC/CD34 AML cell could effectively induce the proliferation and activation of CTLs. However, only the former CTLs could effectively attack AML progenitor cells, and result in the unkilled progenitor/initiating cells losing the abilities of active proliferation in vitro and engraftment in NOD-SCID mice. These findings suggest that AML progenitor/initiating cell-specific CTLs may be generated based on allogeneic DC/progenitor cell fusion strategy; the induced CTLs may potentially eradicate AML by targeting L-ICs directly or indirectly.
authors.affiliation: Department of Biochemistry and Molecular Biology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, The People's Republic of China.
authors.forename: Zhang
authors.initials: Z
authors.lastname: Lei
authors.forename: Gui-Mei
authors.initials: GM
authors.lastname: Zhang
authors.forename: Mei
authors.initials: M
authors.lastname: Hong
authors.forename: Zuo-Hua
authors.initials: ZH
authors.lastname: Feng
authors.forename: Bo
authors.initials: B
authors.lastname: Huang