J. Exp. Med.
© The Rockefeller University Press
0022-1007/97/10/1247/10 $2.00
Volume 186, Number 8, October 20, 1997 1247-1256

Dendritic Cells Genetically Modified with an Adenovirus Vector Encoding the cDNA for a Model Antigen Induce Protective and Therapeutic Antitumor Immunity

By Wenru Song,^* Hwai-Loong Kong,^* Heather Carpenter,^* Hideshi Torii, Richard Granstein, Shahin Rafii,^§ Malcolm A.S. Moore, and Ronald G. Crystal^*

From the ^* Division of Pulmonary and Critical Care Medicine,  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

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 -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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