Hartman Institute for Therapeutic Organ Regeneration

Dendritic cells genetically modified with an adenovirus vector encoding the cDNA for a model antigen induce protective and therapeutic antitumor immunity.

TitleDendritic cells genetically modified with an adenovirus vector encoding the cDNA for a model antigen induce protective and therapeutic antitumor immunity.
Publication TypeJournal Article
Year of Publication1997
AuthorsSong W, Kong HL, Carpenter H, Torii H, Granstein R, Rafii S, Moore MA, Crystal RG
JournalJ Exp Med
Volume186
Issue8
Pagination1247-56
Date Published1997 Oct 20
ISSN0022-1007
KeywordsAdenocarcinoma, Adenoviridae, Animals, beta-Galactosidase, Bone Marrow Cells, Bone Marrow Transplantation, Cell Line, Colonic Neoplasms, Dendritic Cells, DNA, Complementary, Gene Transfer Techniques, Genetic Vectors, Humans, Immunotherapy, Adoptive, Lung Neoplasms, Lymphocyte Activation, Male, Mice, Mice, Inbred BALB C, Models, Immunological, Neoplasm Transplantation, T-Lymphocytes, Cytotoxic
Abstract

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 beta-galactosidase (betagal) 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 betagal, 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.

DOI10.1084/jem.186.8.1247
Alternate JournalJ Exp Med
PubMed ID9334364
PubMed Central IDPMC2199096
Grant ListK08-HL 02926 / HL / NHLBI NIH HHS / United States
R01-AR 40667 / AR / NIAMS NIH HHS / United States

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