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

Wenru Song, Hwai Loong Kong, Heather Carpenter, Hideshi Torii, Richard Granstein, Shahin Rafii, Malcolm A.S. Moore, Ronald Crystal

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350 Citations (Scopus)

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 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.

Original languageEnglish
Pages (from-to)1247-1256
Number of pages10
JournalJournal of Experimental Medicine
Volume186
Issue number8
DOIs
Publication statusPublished - 20 Oct 1997
Externally publishedYes

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ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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