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 β-galactosidase (βgal) 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 βgal, 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.
Dendritic Cells Genetically Modified with an Adenovirus Vector Encoding the cDNA for a Model Antigen Induce Protective and Therapeutic Antitumor Immunity
Address correspondence to Ronald G. Crystal, Division of Pulmonary and Critical Care Medicine, The New York Hospital–Cornell Medical Center, 520 East 70th Street, ST505, New York, New York 10021. Phone: 212-746-2258; FAX: 212-748-8383; E-mail: [email protected]
These studies were supported, in part, by GenVec, Inc. (Rockville, MD) and the Will Rogers Memorial Fund (White Plains, NY). M.A.S. Moore is supported by the Gar Reichman Fund of the Cancer Research Institute (New York), S. Rafii is supported by a grant from the National Institutes of Health (K08-HL 02926), and Dorothy Rodbell Foundation for Sarcoma Research, (New York), R. Granstein is supported by a grant from the National Institutes of Health (R01-AR 40667) and a grant from the Edith C. Blum Foundation (New York), H.-L. Kong is supported, in part, by the Ministry of Health of Singapore, the Singapore National Medical Research Council, and the National University Hospital (Singapore, Republic of Singapore).
W. Song and H.-L. Kong participated equally in this study.
Abbreviations used in this paper: Ad, adenovirus; βgal, β galactosidase; DC, dendritic cell; moi, multiplicity of infection.
Wenru Song, Hwai-Loong Kong, Heather Carpenter, Hideshi Torii, Richard Granstein, Shahin Rafii, Malcolm A.S. Moore, Ronald G. Crystal; Dendritic Cells Genetically Modified with an Adenovirus Vector Encoding the cDNA for a Model Antigen Induce Protective and Therapeutic Antitumor Immunity . J Exp Med 20 October 1997; 186 (8): 1247–1256. doi: https://doi.org/10.1084/jem.186.8.1247
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