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 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.
University of Minnesota Cancer Center and Department of Pediatrics, Division of Bone Marrow Transplantation, University of Minnesota, Minneapolis, MN 55455, USA.
A B
AB
Pawlowska
S
S
Hashino
H
H
McKenna
B J
BJ
Weigel
P A
PA
Taylor
B R
BR
Blazar
D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D000917:Antibody Formation / Q000528:radiation effects; D016026:Bone Marrow Transplantation; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology / Q000637:transplantation*; D006410:Hematopoiesis / Q000187:drug effects; D016219:Immunotherapy, Adoptive; D007694:Killer Cells, Natural / Q000276:immunology; D015470:Leukemia, Myeloid, Acute / Q000517:prevention & control / Q000628:therapy*; D008565:Membrane Proteins / Q000008:administration & dosage / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009368:Neoplasm Transplantation; D014185:Transplantation, Isogeneic; D014407:Tumor Cells, Cultured / Q000637:transplantation
D000276:Adjuvants, Immunologic; D008565:Membrane Proteins; C084881:flt3 ligand protein