Lei Zhang, Zhang Gui-Mei, Hong Mei, Feng Zuo-Hua, Huang Bo
Department of Biochemistry and Molecular Biology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, The People's Republic of China.
J Immunother. 2009 May;32(4):408-14. doi: 10.1097/CJI.0b013e3181a01abb.
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.
独特的白血病起始细胞（L-ICs）是急性髓系白血病（AML）治疗干预的关键靶点。根除L-ICs的一种潜在策略是产生L-IC特异性细胞毒性T淋巴细胞（CTLs）。然而，由于L-ICs的稀有性和永生性，抗原呈递细胞很难捕获L-ICs进行特异性抗原呈递。在此，我们报告了一种通过融合异基因树突状细胞（DCs）和CD34CD38 AML祖细胞的新方法，通过该方法可有效诱导特异性CTLs，导致对AML起始细胞的细胞溶解。DC/CD34CD38 AML细胞或DC/CD34 AML细胞的融合均可有效诱导CTLs的增殖和活化。然而，只有前者的CTLs能有效攻击AML祖细胞，并导致未被杀死的祖细胞/起始细胞在体外失去活跃增殖能力以及在NOD-SCID小鼠体内失去植入能力。这些发现表明，基于异基因DC/祖细胞融合策略可能产生AML祖细胞/起始细胞特异性CTLs；诱导产生的CTLs可能通过直接或间接靶向L-ICs来潜在根除AML。
