Suppression of in vivo tumorigenicity of human lung cancer cells by retrovirus-mediated transfer of the human tumor necrosis factor-alpha cDNA. Academic Article uri icon

Overview

MeSH

  • Animals
  • Base Sequence
  • Cell Division
  • DNA, Complementary
  • DNA, Neoplasm
  • Female
  • Gene Expression Regulation, Neoplastic
  • Genetic Therapy
  • Genetic Vectors
  • Humans
  • Male
  • Mice
  • Mice, Nude
  • Molecular Sequence Data
  • Moloney murine leukemia virus
  • Tumor Cells, Cultured

MeSH Major

  • Gene Transfer Techniques
  • Lung Neoplasms
  • Tumor Necrosis Factor-alpha

abstract

  • The clinical use of tumor necrosis factor-alpha (TNF) is constrained by tumor cell resistance and systemic toxicity. Based on observations with murine tumors, we hypothesized that induction of local TNF production by the tumor may suppress growth of human cancer cells. To evaluate this, a human TNF cDNA was transferred to human lung cancer cell lines in vitro using a retrovirus vector to produce TNF cDNA-modified cell lines secreting TNF. In vitro cell growth was similar for parental and modified cells. All cells were resistant to TNF. The in vivo tumorigenicity of parental and modified cells was compared in nude mice. Animals injected subcutaneously with parental cells uniformly developed tumors. Tumor growth was markedly less for all modified cells, and this suppression of tumor development was reversed by anti-TNF antibody administration. Animals injected with a mixture of 50% modified and 50% parental cells or parental cell tumors injected with modified cells had decreased tumor growth, demonstrating that modified cells could suppress tumorigenicity. These data suggest that TNF can induce antitumor defenses to suppress in vivo human tumor cell growth and provide a rationale for transferring the human TNF cDNA directly to malignant cells for the therapy of human lung cancer.

publication date

  • September 1994

has subject area

  • Animals
  • Base Sequence
  • Cell Division
  • DNA, Complementary
  • DNA, Neoplasm
  • Female
  • Gene Expression Regulation, Neoplastic
  • Gene Transfer Techniques
  • Genetic Therapy
  • Genetic Vectors
  • Humans
  • Lung Neoplasms
  • Male
  • Mice
  • Mice, Nude
  • Molecular Sequence Data
  • Moloney murine leukemia virus
  • Tumor Cells, Cultured
  • Tumor Necrosis Factor-alpha

Research

keywords

  • Journal Article

Identity

Language

  • eng

Digital Object Identifier (DOI)

  • 10.1165/ajrcmb.11.3.8086165

PubMed ID

  • 8086165

Additional Document Info

start page

  • 270

end page

  • 278

volume

  • 11

number

  • 3