Fibroblasts genetically engineered to secrete cytokines suppress tumor growth and induce antitumor immunity to a murine glioma in vivo

Roberta P. Glick, Terry Lichtor, Tae Sung Kim, Saraja Ilangovan, Edward P. Cohen

Research output: Contribution to journalArticle

48 Citations (Scopus)

Abstract

THE GENES FOR interleukin (IL)-2, interferon (IFN)-γ, or both IL-2 and IFN-γ were introduced into a mouse fibroblast cell line (LM) expressing defined major histocompatibility complex determinants (H-2k). The cytokine-secreting cells were then co-transplanted with the Gl261 murine glioma cell line (H-2b) into syngeneic C57BL/6 mice that differed at the major histocompatibility complex from the cytokine-secreting cells. The period of survival of mice with glioma treated with IL-2- or IL-2/IFN-γ-secreting allogeneic cells was significantly prolonged (P <0.025) relative to the survival of mice receiving equivalent numbers of tumor cells alone or mice with glioma treated with nonsecreting fibroblast (LM) cells. Gliomas in the treated mice had an extensive lymphocytic cell infiltrate. Using a 51Cr release assay, the specific release of isotope from labeled Gl261 cells co-incubated with spleen cells from mice injected with the glioma cells and IL-2-secreting fibroblasts was higher (P <0.001) than the release from glioma cells co-incubated with spleen cells from nonimmunized mice. Significantly higher levels of release (P <0.005) were found in the group immunized with fibroblasts secreting both IL-2 and IFN-γ. Based upon the effect of monoclonal antibodies for T-cell subsets on the antiglioma response, the immunity was mediated predominantly by natural killer/lymphokine-activated killer cells.

Original languageEnglish
Pages (from-to)548-555
Number of pages8
JournalNeurosurgery
Volume36
Issue number3
Publication statusPublished - 1995
Externally publishedYes

Fingerprint

Glioma
Immunity
Fibroblasts
Cytokines
Interleukin-2
Growth
Neoplasms
Interferons
Major Histocompatibility Complex
Spleen
Lymphokine-Activated Killer Cells
Cell Line
T-Lymphocyte Subsets
Inbred C57BL Mouse
Isotopes
Cell Count
Monoclonal Antibodies

Keywords

  • Gene therapy
  • Glioma
  • Interferon-γ
  • Interleukin-2

ASJC Scopus subject areas

  • Clinical Neurology
  • Surgery

Cite this

Fibroblasts genetically engineered to secrete cytokines suppress tumor growth and induce antitumor immunity to a murine glioma in vivo. / Glick, Roberta P.; Lichtor, Terry; Kim, Tae Sung; Ilangovan, Saraja; Cohen, Edward P.

In: Neurosurgery, Vol. 36, No. 3, 1995, p. 548-555.

Research output: Contribution to journalArticle

Glick, Roberta P. ; Lichtor, Terry ; Kim, Tae Sung ; Ilangovan, Saraja ; Cohen, Edward P. / Fibroblasts genetically engineered to secrete cytokines suppress tumor growth and induce antitumor immunity to a murine glioma in vivo. In: Neurosurgery. 1995 ; Vol. 36, No. 3. pp. 548-555.
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