Persistent, antigen-specific, therapeutic antitumor immunity by dendritic cells genetically modified with an adenoviral vector to express a model tumor antigen.
Dendritic cells (DC) are potent antigen-presenting cells that play a critical role in the initiation of cellular immune responses. Using a BALB/c syngeneic colon carcinoma cell line expressing a model tumor antigen beta-galactosidase (betagal), we previously reported (Song et al, J Exp Med 1997; 186: 1247-1256) that immunization of mice with a single injection of DCs genetically modified with an adenovirus vector expressing betagal confers potent protection against a lethal intravenous tumor challenge, as well as suppression of pre-established lung tumors, resulting in a significant survival advantage. In the present study, we have addressed the question: how long does the memory of tumor antigen- specific immunity persists after DC priming in vivo using this genetically modified DC-based cancer vaccination strategy? To accomplish this, two groups of mice were evaluated: (1) mice surviving >400 days following protection from an initial intravenous tumor challenge after immunization with DC genetically modified to express betagal; and (2) mice surviving >300 days that had previously demonstrated regression of pre-established lung tumors after treatment with DC immunization. By analyzing the antigen-specific cytotoxic T lymphocyte response and challenging these long-term survival mice with a second subcutaneous tumor administration, the data demonstrate that a single administration of DC genetically modified to express a model antigen induces long-lasting, antigen-specific antitumor immunity in both naive and tumor-bearing hosts, observations that have important implications in the development of genetically modified DC-based antitumor vaccination strategies. Gene Therapy (2000) 7, 2080-2086.
Division of Pulmonary and Critical Care Medicine, Weill Medical College of Cornell University, New York, NY, USA.
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Song
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Tong
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Carpenter
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Kong
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Crystal
D000256:Adenoviridae / Q000235:genetics; D019264:Adoptive Transfer / Q000379:methods*; D000818:Animals; D000951:Antigens, Neoplasm / Q000235:genetics*; D003110:Colonic Neoplasms / Q000276:immunology / Q000628:therapy*; D003713:Dendritic Cells / Q000276:immunology*; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000008:administration & dosage; D007156:Immunologic Memory; D008175:Lung Neoplasms / Q000276:immunology / Q000556:secondary / Q000628:therapy; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D013997:Time Factors; D001616:beta-Galactosidase / Q000235:genetics / Q000276:immunology
D000951:Antigens, Neoplasm; D001616:beta-Galactosidase