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Blood, 1 March 2002, Vol. 99, No. 5, pp. 1676-1682
IMMUNOBIOLOGY
In vivo manipulation of dendritic cells to induce
therapeutic immunity
Miriam Merad,
Tomoharu Sugie,
Edgar G. Engleman, and
Lawrence Fong
From the Department of Pathology, Stanford University
School of Medicine, Stanford, CA.
Efficient antigen presentation and T-cell priming are essential
components of effective antitumor immunity. Dendritic cells are
critical to both of these functions but to date no method has been
devised that both targets antigen to these cells and activates them, in
situ, in a manner that induces systemic immunity. In this study we
combined a dendritic cell growth factor, Flt3 ligand, with a dendritic
cell activator, immunostimulatory DNA, and a tumor antigen to activate
and load dendritic cells in vivo. Initial studies showed that
immunostimulatory DNA not only activates dendritic cells but also
prolongs their survival in vivo and in vitro. Following treatment of
mice with Flt3 ligand, coadministration of immunostimulatory DNA and
antigen induced potent antitumor immunity, resulting in both tumor
prevention and regression of existing tumors. CD8 cytotoxic T
lymphocytes but not CD4 T cells were required for tumor protection.
Natural killer cells also contributed to tumor protection. These
results show that dendritic cells can be loaded with antigen and
activated, in situ, and provide the basis for dendritic cell- targeted
clinical strategies.
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