Treatment with allogeneic interleukin-2 secreting fibroblasts protects against the development of malignant brain tumors

Roberta P. Glick, Terry Lichtor, Ripul Panchal, Anjuli Mahendra, Edward P. Cohen

Research output: Contribution to journalArticle

14 Scopus citations

Abstract

We have reported that mice with an intracerebral (i.e.) malignant glioma or breast cancer treated with i.e. injection of allogeneic fibroblasts genetically engineered to secrete interleukin-2 (IL-2) survived longer than mice in various control groups. The goal of the present study was to determine the effectiveness of utilizing IL-2 secreting allogeneic fibroblasts as a protective treatment to prevent the development of an i.c. glioma or breast carcinoma. Using an intracranial microcannula system that we developed, the animals received weekly injections of the cellular vaccine prior to the introduction of tumor cells via the cannula. The results demonstrate a significant delay (P < 0.005) in the development of glioma in the animals pre-treated with either allogeneic non-secreting or IL-2-secreting fibroblasts prior to introduction of tumor cells. In addition, 50% of the animals pre-treated with IL-2 secreting allogeneic fibroblasts injected subsequently with G1261 glioma cells did not develop a tumor, while all of the animals injected with glioma cells alone and 92% of those treated with non-secreting fibroblasts eventually died. The long-term survivors from the pre-treatment group were subsequently re-challenged with tumor and compared to naïve controls. There was evidence that long-term immunity was established in the pre-treated animals, since there was a significant prolongation of survival (P < 0.01). In similar experiments using breast cancer cells, 62% of the animals pretreated with non-secreting allogeneic fibroblasts and 75% of the animals pre-treated with allogeneic IL-2 secreting fibroblasts subsequently injected with SB-5b breast carcinoma cells did not develop tumors and had a significant prolongation of survival. These data suggest that i.c. injection of allogeneic IL-2 secreting fibroblasts are effective as a protective treatment in the prevention of the development of a brain tumor when the fibroblasts are introduced into the same site where the tumor is subsequently injected.

Original languageEnglish (US)
Pages (from-to)139-146
Number of pages8
JournalJournal of Neuro-Oncology
Volume64
Issue number1-2
DOIs
StatePublished - Aug 2003
Externally publishedYes

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Keywords

  • Cytokine
  • Gene therapy
  • Interleukin-2
  • Tumor vaccine

ASJC Scopus subject areas

  • Clinical Neurology
  • Cancer Research
  • Oncology
  • Neuroscience(all)

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