In vitro tumor-pulsed or in vivo Flt3 ligand-generated dendritic cells provide protection against acute myelogenous leukemia in nontransplanted or syngeneic bone marrow-transplanted mice

To determine whether immune stimulation could reduce acute myelogenous leuk emia (AML) lethality, dendritic cells (DCs) were pulsed with AML antigens a nd used as vaccines or generated in vivo by Flt3 ligand (Flt3L), a potent s timulator of DC and natural killer (NK) cell generation. Mice were then cha llenged with ANLL cells. The total number of splenic anti-AML cytotoxic T-l ymphocyte 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 com pared 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 antitumo r responses of Flt3L or DCs, respectively. DC vaccines lead to long-term me mory responses but Flt3L does not, Syngeneic bone marrow transplantation (B MT) recipients were analyzed beginning 2 months post-BMT in contrast to the uniform lethality in BMT controls given AML cells, recipients of either Fl t3L 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 increa sed the total anti-AML CTLPs 1.4-fold and 6.8-fold, respectively. Neither a pproach was successful when initiated after AML challenge. It was concluded that DC vaccines and Flt3L administration can enhance an AML response in n on-transplanted or syngeneic BMT mice but only when initiated prior to AML progression. (Blood, 2001;97:1474-1482) (C) 2001 by The American Society of Hematology.