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Blood, 1 March 2001, Vol. 97, No. 5, pp. 1474-1482
TRANSPLANTATION
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
Anna B. Pawlowska,
Satoshi Hashino,
Hilary McKenna,
Brenda J. Weigel,
Patricia A. Taylor, and
Bruce R. Blazar
From the University of Minnesota Cancer Center and
Department of Pediatrics, Division of Bone Marrow Transplantation,
University of Minnesota, Minneapolis, MN, and Immunex Corporation,
Seattle, WA.
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.
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