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  • Acquired Diseases
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Persistent, antigen-specific, therapeutic antitumor immunity by dendritic cells genetically modified with an adenoviral vector to express a model tumor antigen

Gene Therapy volume 7, pages 2080–2086 (2000)Cite this article

Abstract

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 β-galactosidase (βgal), 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 βgal 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 βgal; 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.

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Acknowledgements

We thank N Mohamed in helping to prepare this manuscript. These studies were supported, in part, by the National Cancer Institute R01 CA75192; Will Rogers Memorial Fund, Los Angeles, CA; and GenVec, Inc., Rockville, MD.

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Authors and Affiliations

  1. Division of Pulmonary and Critical Care Medicine, Weill Medical College of Cornell University, New York, NY, USA

    W Song, Y Tong, H Carpenter, H-L Kong & R G Crystal

  2. Institute of Genetic Medicine, Weill Medical College of Cornell University, New York, NY, USA

    R G Crystal

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  1. W Song
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  2. Y Tong
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  3. H Carpenter
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  4. H-L Kong
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  5. R G Crystal
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Song, W., Tong, Y., Carpenter, H. et al. Persistent, antigen-specific, therapeutic antitumor immunity by dendritic cells genetically modified with an adenoviral vector to express a model tumor antigen. Gene Ther 7, 2080–2086 (2000). https://doi.org/10.1038/sj.gt.3301336

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