Persistent, antigen-specific, therapeutic antitumor immunity by dendritic cells genetically modified with an adenoviral vector to express a model tumor antigen. Academic Article uri icon

Overview

MeSH

  • Adenoviridae
  • Animals
  • Genetic Vectors
  • Immunologic Memory
  • Lung Neoplasms
  • Male
  • Mice
  • Mice, Inbred BALB C
  • T-Lymphocytes, Cytotoxic
  • Time Factors
  • beta-Galactosidase

MeSH Major

  • Adoptive Transfer
  • Antigens, Neoplasm
  • Colonic Neoplasms
  • Dendritic Cells
  • Genetic Therapy

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.

publication date

  • December 2000

has subject area

  • Adenoviridae
  • Adoptive Transfer
  • Animals
  • Antigens, Neoplasm
  • Colonic Neoplasms
  • Dendritic Cells
  • Genetic Therapy
  • Genetic Vectors
  • Immunologic Memory
  • Lung Neoplasms
  • Male
  • Mice
  • Mice, Inbred BALB C
  • T-Lymphocytes, Cytotoxic
  • Time Factors
  • beta-Galactosidase

Research

keywords

  • Journal Article

Identity

Language

  • eng

Digital Object Identifier (DOI)

  • 10.1038/sj.gt.3301336

PubMed ID

  • 11223988

Additional Document Info

start page

  • 2080

end page

  • 2086

volume

  • 7

number

  • 24