Xing D, Decker W K, Li S, Robinson S N, Yang H, Segal H, O'Connor S, Yao X, Komanduri K V, McMannis J D, Jones R B, de Lima M, Champlin R E, Shpall E J
The University of Texas MD Anderson Cancer Center, Department of Blood and Marrow Transplantation, Houston, Texas 77030, USA.
Cytotherapy. 2006;8(2):95-104. doi: 10.1080/14653240600620093.
The generation of AML-specific T-lymphocyte responses by leukemia-derived DC has been documented by multiple investigators and is being pursued clinically. An obstacle to widespread use of this strategy is that it has not been possible to generate leukemic DC from all patients, and an alternative approach is needed if the majority of leukemia patients are to receive therapeutic vaccination in conjunction with other treatment protocols.
In the present study, we generated DC from CD14-selected monocytes isolated from healthy donor PBPC and loaded them with a total cell lysate from AML patient blasts.
Immature in vitro-derived DC exhibited robust phagocytic activity, and mature DC demonstrated high expression of CD80, CD83, CD86 and the chemokine receptor CCR7, important for DC migration to local lymph nodes. Mature, Ag-loaded DC were used as APC for leukemia-specific cytotoxic T-lymphocyte (CTL) induction and demonstrated cytotoxic activity against leukemic targets. CTL lysis was Ag-specific, with killing of both allogeneic leukemic blasts and autologous DC loaded with allogeneic AML lysate. HLA-matched controls were not lysed in our system.
These data support further research into the use of this strategy as an alternative approach to leukemia-derived DC vaccination.
多位研究者已证明白血病来源的树突状细胞（DC）可产生急性髓系白血病（AML）特异性T淋巴细胞反应，并且该反应正在进行临床研究。广泛应用此策略的一个障碍是无法从所有患者中产生白血病DC，如果要让大多数白血病患者在接受其他治疗方案的同时接受治疗性疫苗接种，就需要一种替代方法。
在本研究中，我们从健康供体外周血祖细胞中分离出经CD14选择的单核细胞，从中生成DC，并将其用AML患者原始细胞的全细胞裂解物进行负载。
体外衍生的未成熟DC表现出强大的吞噬活性，成熟DC显示出CD80、CD83、CD86和趋化因子受体CCR7的高表达，这些对于DC迁移至局部淋巴结很重要。成熟的、负载抗原的DC用作诱导白血病特异性细胞毒性T淋巴细胞（CTL）的抗原呈递细胞（APC），并显示出对白血病靶标的细胞毒性活性。CTL裂解具有抗原特异性，可杀死同种异体白血病原始细胞和负载同种异体AML裂解物的自体DC。在我们的系统中，HLA匹配的对照未被裂解。
这些数据支持进一步研究将此策略作为白血病来源的DC疫苗接种的替代方法。
