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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.

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 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.
AuthorsW Song, Y Tong, H Carpenter, H L Kong, R G Crystal
JournalGene therapy (Gene Ther) Vol. 7 Issue 24 Pg. 2080-6 (Dec 2000) ISSN: 0969-7128 [Print] England
PMID11223988 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
Chemical References
  • Antigens, Neoplasm
  • beta-Galactosidase
Topics
  • Adenoviridae (genetics)
  • Adoptive Transfer (methods)
  • Animals
  • Antigens, Neoplasm (genetics)
  • Colonic Neoplasms (immunology, therapy)
  • Dendritic Cells (immunology)
  • Genetic Therapy (methods)
  • Genetic Vectors (administration & dosage)
  • Immunologic Memory
  • Lung Neoplasms (immunology, secondary, therapy)
  • Male
  • Mice
  • Mice, Inbred BALB C
  • T-Lymphocytes, Cytotoxic (immunology)
  • Time Factors
  • beta-Galactosidase (genetics, immunology)

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