Dendritic cells genetically modified with an adenovirus vector encoding the cDNA for a model antigen induce protective and therapeutic antitumor immunity. Academic Article uri icon

Overview

MeSH

  • Animals
  • Bone Marrow Cells
  • Bone Marrow Transplantation
  • Cell Line
  • Gene Transfer Techniques
  • Genetic Vectors
  • Humans
  • Lung Neoplasms
  • Lymphocyte Activation
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Models, Immunological
  • Neoplasm Transplantation
  • T-Lymphocytes, Cytotoxic

MeSH Major

  • Adenocarcinoma
  • Adenoviridae
  • Colonic Neoplasms
  • DNA, Complementary
  • Dendritic Cells
  • Immunotherapy, Adoptive
  • beta-Galactosidase

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 beta-galactosidase (betagal) 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 betagal, 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.

publication date

  • October 20, 1997

has subject area

  • Adenocarcinoma
  • Adenoviridae
  • Animals
  • Bone Marrow Cells
  • Bone Marrow Transplantation
  • Cell Line
  • Colonic Neoplasms
  • DNA, Complementary
  • Dendritic Cells
  • Gene Transfer Techniques
  • Genetic Vectors
  • Humans
  • Immunotherapy, Adoptive
  • Lung Neoplasms
  • Lymphocyte Activation
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Models, Immunological
  • Neoplasm Transplantation
  • T-Lymphocytes, Cytotoxic
  • beta-Galactosidase

Research

keywords

  • Journal Article

Identity

Language

  • eng

PubMed Central ID

  • PMC2199096

PubMed ID

  • 9334364

Additional Document Info

start page

  • 1247

end page

  • 1256

volume

  • 186

number

  • 8