Paracrine delivery of IL-12 against intracranial 9L gliosarcoma in rats

Francesco Dimeco, Laurence D. Rhines, Justin Hanes, Betty M. Tyler, Daniel Brat, Elena Torchiana, Michael Guarnieri, Mario P. Colombo, Drew M. Pardoll, Gaetano Finocchiaro, Henry Brem, Alessandro Olivi

Research output: Contribution to journalArticle

55 Citations (Scopus)

Abstract

Object. Interleukin-12 (IL-12) has potential for the treatment of tumors because it can stimulate an antitumor immune response and possesses antiangiogenic properties. In the study reported here, the authors investigated the therapeutic role of locally delivered Il-12 in a malignant brain tumor model. Methods. After genetically engineering 9L gliosarcoma cells to express IL-12 (9L-IL12 cells), the authors used these cells as a source of locally delivered cytokine. First, they investigated the behavior of these cells, which were implanted with the aid of stereotactic guidance into the rat brain, by using serial magnetic resonance imaging and histopathological examination. Second, they assessed the antitumor efficacy of proliferating, as well as nonproliferating (irradiated), 9L-IL12 cells by implanting these cells in animals challenged by wild-type 9l gliosarcoma (9Lwt) cells. The IL-12 expression in brain regions injected with 9L-IL12 was confirmed by reverse transcription-polymerase chain reaction. Last, the authors explored whether animals treated with 9L-IL12 cells developed an antitumor immunological memory by rechallenging the survivors with a second injection of 9Lwt cells. The authors demonstrated that local delivery of IL-12 into the rat brain by genetically engineered cells significantly prolongs survival time in animals challenged intracranially with a malignant glioma. Conclusions. These findings support continued efforts to refine local delivery systems of IL-12 in an attempt to bring this therapy to clinical trials.

Original languageEnglish
Pages (from-to)419-427
Number of pages9
JournalJournal of Neurosurgery
Volume92
Issue number3
Publication statusPublished - Mar 2000

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Gliosarcoma
Interleukin-12
Brain
Immunologic Memory
Wild Animals
Brain Neoplasms
Glioma
Reverse Transcription
Therapeutics

Keywords

  • Brain neoplasm
  • Cytokine
  • Glioma
  • Immunotherapy
  • Interleukin-12
  • Rat

ASJC Scopus subject areas

  • Clinical Neurology
  • Neuroscience(all)

Cite this

Dimeco, F., Rhines, L. D., Hanes, J., Tyler, B. M., Brat, D., Torchiana, E., ... Olivi, A. (2000). Paracrine delivery of IL-12 against intracranial 9L gliosarcoma in rats. Journal of Neurosurgery, 92(3), 419-427.

Paracrine delivery of IL-12 against intracranial 9L gliosarcoma in rats. / Dimeco, Francesco; Rhines, Laurence D.; Hanes, Justin; Tyler, Betty M.; Brat, Daniel; Torchiana, Elena; Guarnieri, Michael; Colombo, Mario P.; Pardoll, Drew M.; Finocchiaro, Gaetano; Brem, Henry; Olivi, Alessandro.

In: Journal of Neurosurgery, Vol. 92, No. 3, 03.2000, p. 419-427.

Research output: Contribution to journalArticle

Dimeco, F, Rhines, LD, Hanes, J, Tyler, BM, Brat, D, Torchiana, E, Guarnieri, M, Colombo, MP, Pardoll, DM, Finocchiaro, G, Brem, H & Olivi, A 2000, 'Paracrine delivery of IL-12 against intracranial 9L gliosarcoma in rats', Journal of Neurosurgery, vol. 92, no. 3, pp. 419-427.
Dimeco F, Rhines LD, Hanes J, Tyler BM, Brat D, Torchiana E et al. Paracrine delivery of IL-12 against intracranial 9L gliosarcoma in rats. Journal of Neurosurgery. 2000 Mar;92(3):419-427.
Dimeco, Francesco ; Rhines, Laurence D. ; Hanes, Justin ; Tyler, Betty M. ; Brat, Daniel ; Torchiana, Elena ; Guarnieri, Michael ; Colombo, Mario P. ; Pardoll, Drew M. ; Finocchiaro, Gaetano ; Brem, Henry ; Olivi, Alessandro. / Paracrine delivery of IL-12 against intracranial 9L gliosarcoma in rats. In: Journal of Neurosurgery. 2000 ; Vol. 92, No. 3. pp. 419-427.
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AB - Object. Interleukin-12 (IL-12) has potential for the treatment of tumors because it can stimulate an antitumor immune response and possesses antiangiogenic properties. In the study reported here, the authors investigated the therapeutic role of locally delivered Il-12 in a malignant brain tumor model. Methods. After genetically engineering 9L gliosarcoma cells to express IL-12 (9L-IL12 cells), the authors used these cells as a source of locally delivered cytokine. First, they investigated the behavior of these cells, which were implanted with the aid of stereotactic guidance into the rat brain, by using serial magnetic resonance imaging and histopathological examination. Second, they assessed the antitumor efficacy of proliferating, as well as nonproliferating (irradiated), 9L-IL12 cells by implanting these cells in animals challenged by wild-type 9l gliosarcoma (9Lwt) cells. The IL-12 expression in brain regions injected with 9L-IL12 was confirmed by reverse transcription-polymerase chain reaction. Last, the authors explored whether animals treated with 9L-IL12 cells developed an antitumor immunological memory by rechallenging the survivors with a second injection of 9Lwt cells. The authors demonstrated that local delivery of IL-12 into the rat brain by genetically engineered cells significantly prolongs survival time in animals challenged intracranially with a malignant glioma. Conclusions. These findings support continued efforts to refine local delivery systems of IL-12 in an attempt to bring this therapy to clinical trials.

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