| 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. |
| Keywords: |
survival; controlled study; nonhuman; adenocarcinoma; animal cell; mouse; animals; mice; animal tissue; bone marrow cells; gene expression; dendritic cell; lung neoplasms; cell line; animal model; colonic neoplasms; mice, inbred balb c; gene transfer; genetic vectors; lymphocyte activation; dendritic cells; immune response; antigen; cytotoxic t lymphocyte; t-lymphocytes, cytotoxic; newborn; beta galactosidase; tumor immunity; neoplasm transplantation; tumor; bone marrow transplantation; antigen presenting cell; immunotherapy, adoptive; complementary dna; adenoviridae; dna, complementary; virus vector; gene transfer techniques; immunization; beta-galactosidase; adenovirus; major histocompatibility antigen; models, immunological; humans; male; priority journal; article
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