Cationic lipid gene transfer of an IL-2 transgene leads to activation of natural killer cells in a SCID mouse human tumor xenograft

Paul R. Clark, Alison T Stopeck, Suezanne E. Parker, Evan M Hersh

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Natural killer (NK) cells play an important role in combating infectious and malignant diseases and interleukin-2 (IL-2) has been shown to promote proliferation and activation of NK cells in vitro and in vivo. Here we investigate the effects of local cationic lipid-mediated IL-2 gene transfer on intratumoral accumulation and activation of NK cells in a SCID mouse tumor model. UM449 human melanoma tumors in SCID mice received intratumoral injections of DMRIE/ DOPE admixed with VR1103, a DNA plasmid encoding the gene for human IL-2. Dissagregated tumor cells were tested for IL-2 secretion and were characterized using antibodies to asGM1, MAC-1, and F4/80 antigens. Granzyme A, a proteolytic serine esterase, was also measured in tumor cell lysates. IL-2 secretion from tumors injected with VR1103:DMRIE/DOPE peaked at 48 h after injection and fell to baseline levels on day 8. Intratumoral granzyme A activity was significantly increased in tumors injected with IL-2 plasmid:DMRIE/ DOPE complexes, but not by an irrelevant plasmid DNA:DMRIE/DOPE control. Importantly, the growth of UM449 tumors was slowed in VR1103:DMRIE/DOPE-injected tumors. These results indicate that local cationic lipid-mediated gene transfer of IL-2 induces activation of intratumoral NK cells and slows tumor growth. (C) 2000 Academic Press.

Original languageEnglish (US)
Pages (from-to)96-104
Number of pages9
JournalCellular Immunology
Volume204
Issue number2
DOIs
StatePublished - Sep 15 2000

Fingerprint

SCID Mice
Transgenes
Heterografts
Natural Killer Cells
Interleukin-2
Lipids
Genes
Neoplasms
Granzymes
Plasmids
Injections
DNA
Growth
Communicable Diseases
Melanoma
(3-dimyristyloxypropyl)(dimethyl)(hydroxyethyl)ammonium
Antibodies

Keywords

  • Cationic lipid
  • Granzyme A
  • Interleukin-2
  • Intratumoral
  • Natural killer cell
  • Tumor

ASJC Scopus subject areas

  • Cell Biology
  • Immunology

Cite this

Cationic lipid gene transfer of an IL-2 transgene leads to activation of natural killer cells in a SCID mouse human tumor xenograft. / Clark, Paul R.; Stopeck, Alison T; Parker, Suezanne E.; Hersh, Evan M.

In: Cellular Immunology, Vol. 204, No. 2, 15.09.2000, p. 96-104.

Research output: Contribution to journalArticle

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