Pawlowska A B, Hashino S, McKenna H, Weigel B J, Taylor P A, Blazar B R
University of Minnesota Cancer Center and Department of Pediatrics, Division of Bone Marrow Transplantation, University of Minnesota, Minneapolis, MN 55455, USA.
Blood. 2001 Mar 1;97(5):1474-82. doi: 10.1182/blood.v97.5.1474.
To determine whether immune stimulation could reduce acute myelogenous leukemia (AML) lethality, dendritic cells (DCs) were pulsed with AML antigens and used as vaccines or generated in vivo by Flt3 ligand (Flt3L), a potent stimulator of DC and natural killer (NK) cell generation. Mice were then challenged with AML cells. The total number of splenic anti-AML cytotoxic T-lymphocyte precursors (CTLPs) present at the time of challenge was increased 1.9-fold and 16.4-fold by Flt3L or DC tumor vaccines, respectively. As compared with the 0% survival of controls, 63% or more of recipients of pulsed DCs or Flt3L survived long term. Mice given AML cells prior to DC vaccines or Flt3L had only a slight survival advantage versus non-treated controls. NK cells or NK cells and T cells were found to be involved in the antitumor responses of Flt3L or DCs, respectively. DC vaccines lead to long-term memory responses but Flt3L does not. Syngeneic bone marrow transplantation (BMT) recipients were analyzed beginning 2 months post-BMT. In contrast to the uniform lethality in BMT controls given AML cells, recipients of either Flt3L or DC vaccines had a significant increase in survival. The total number of splenic anti-AML CTLPs at the time of AML challenge in BMT controls was 40% of concurrently analyzed non-BMT controls. Flt3L or DC vaccines increased the total anti-AML CTLPs 1.4-fold and 6.8-fold, respectively. Neither approach was successful when initiated after AML challenge. It was concluded that DC vaccines and Flt3L administration can enhance an AML response in non-transplanted or syngeneic BMT mice but only when initiated prior to AML progression.
为了确定免疫刺激是否能降低急性髓性白血病（AML）的致死率，用AML抗原刺激树突状细胞（DC）并将其用作疫苗，或者通过Flt3配体（Flt3L）在体内生成DC，Flt3L是DC和自然杀伤（NK）细胞生成的有效刺激剂。然后用AML细胞攻击小鼠。攻击时脾脏中抗AML细胞毒性T淋巴细胞前体（CTLPs）的总数通过Flt3L或DC肿瘤疫苗分别增加了1.9倍和16.4倍。与对照组0%的存活率相比，接受脉冲DC或Flt3L的受体中有63%或更多长期存活。在DC疫苗或Flt3L之前给予AML细胞的小鼠与未治疗的对照组相比只有轻微的生存优势。发现NK细胞或NK细胞与T细胞分别参与Flt3L或DC的抗肿瘤反应。DC疫苗可导致长期记忆反应，但Flt3L不能。在同基因骨髓移植（BMT）后2个月开始分析BMT受体。与接受AML细胞的BMT对照组的一致致死率相反，接受Flt3L或DC疫苗的受体存活率显著提高。在AML攻击时，BMT对照组脾脏中抗AML CTLPs的总数是同期分析的非BMT对照组的40%。Flt3L或DC疫苗分别使抗AML CTLPs总数增加了1.4倍和6.8倍。当在AML攻击后开始时，这两种方法都未成功。得出的结论是，DC疫苗和Flt3L给药可以增强未移植或同基因BMT小鼠对AML的反应，但前提是在AML进展之前开始。
