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From the * Division of Pulmonary and Critical Care Medicine, Dendritic cells (DCs) are potent antigen-presenting cells that play a critical role in the initiation
of antitumor immune responses. In this study, we show that genetic modifications of a murine
epidermis-derived DC line and primary bone marrow-derived DCs to express a model antigen
Department of Dermatology, § Division of Hematology-Oncology, The New York Hospital-Cornell Medical Center, New York
10021; and
James Ewing Laboratory of Developmental Hematopoiesis, Memorial Sloan-Kettering
Cancer Center, New York 10021
-galactosidase (
gal) can be achieved through the use of a replication-deficient, recombinant
adenovirus vector, and that the modified DCs are capable of eliciting antigen-specific, MHC-restricted CTL responses. Importantly, using a murine metastatic lung tumor model with syngeneic colon carcinoma cells expressing
gal, we show that immunization of mice with the
genetically modified DC line or bone marrow DCs confers potent protection against a lethal
tumor challenge, as well as suppression of preestablished tumors, resulting in a significant survival advantage. We conclude that genetic modification of DCs to express antigens that are also
expressed in tumors can lead to antigen-specific, antitumor killer cells, with a concomitant resistance to tumor challenge and a decrease in the size of existing tumors.
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