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 Wilson, Amy M. Fulton, John 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 1 1998

Keywords

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

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Neurology
  • Clinical Neurology

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