IL-10 gene transfer to intracranial 9L glioma: Tumor inhibition and cooperation with IL-2

Adam A. Book, Kevin E. Fielding, Namita Kundu, Mary Ann Ann Wilson, Amy M. Fulton, John J Laterra

Research output: Contribution to journalArticle

Abstract

This study examines the effects of interleukin-10 (IL-10) and combination IL-10 + IL-2 gene transfer on experimental brain tumor growth in vivo. 9L gliosarcoma cells were engineered to stably express murine IL-10 (9L-IL-10 cells) and implanted subcutaneously or to the caudate/putamen of syngeneic rats. The growth of tumors expressing IL-10 was substantially reduced compared to that of control tumors (p <0.05). Intracranial tumors expressing IL-10 and IL-2 were established by co-implanting 9L-IL-10 cells with endothelial cells engineered to express IL-2. At 14 days post- implantation, tumors expressing IL-10 + IL-2 were 99% smaller than control- transfected tumors (p <0.0001). This extent of anti-tumor effect could not be achieved by expression of IL-10 or IL-2 alone within tumors. Neither IL- 10 nor a combination of IL-10 + IL-2 gene delivery inhibited tumor growth in severe combined immunodeficient (SCID-Beige) mice (p > 0.05). Immunohistochemical analysis revealed that IL-10 + IL-2 gene delivery markedly increased T-cell infiltration within the striatum ipsilateral to tumor cell implantation. These findings establish that IL-10 expression, particularly in combination with IL-2 expression, can have significant immune-dependent anti-tumor actions within intracranial gliomas.

Original languageEnglish (US)
Pages (from-to)50-59
Number of pages10
JournalJournal of Neuroimmunology
Volume92
Issue number1-2
DOIs
StatePublished - Dec 1998

Fingerprint

Glioma
Interleukin-10
Interleukin-2
Genes
Neoplasms
Gliosarcoma
Putamen
Growth
Brain Neoplasms
T-Lymphocytes

Keywords

  • Anti-tumor immunity
  • Cytokine
  • Gene therapy
  • Neuroimmunology

ASJC Scopus subject areas

  • Immunology
  • Clinical Neurology
  • Immunology and Allergy
  • Neurology

Cite this

IL-10 gene transfer to intracranial 9L glioma : Tumor inhibition and cooperation with IL-2. / Book, Adam A.; Fielding, Kevin E.; Kundu, Namita; Wilson, Mary Ann Ann; Fulton, Amy M.; Laterra, John J.

In: Journal of Neuroimmunology, Vol. 92, No. 1-2, 12.1998, p. 50-59.

Research output: Contribution to journalArticle

Book, Adam A. ; Fielding, Kevin E. ; Kundu, Namita ; Wilson, Mary Ann Ann ; Fulton, Amy M. ; Laterra, John J. / IL-10 gene transfer to intracranial 9L glioma : Tumor inhibition and cooperation with IL-2. In: Journal of Neuroimmunology. 1998 ; Vol. 92, No. 1-2. pp. 50-59.
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