Comparative analysis of paracrine immunotherapy in experimental brain tumors.

M. S. Lesniak, P. Sampath, F. DiMeco, M. P. Viglione, B. M. Tyler, D. M. Pardoll, H. Brem

Research output: Contribution to journalArticle

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Abstract

OBJECT: Local delivery of cytokines has been shown to have a potent antitumor activity against a wide range of malignant brain tumors. In this study, the authors examined the efficacy of treating central nervous system (CNS) tumors by transfecting poorly immunogenic B16/F10 melanoma cells with interleukin (IL)-2, IL-4, or granulocytemacrophage-colony stimulating factor (GM-CSF) gene, and using these cells to deliver the cytokine locally at the site of the CNS tumor. The object was to determine which cytokine would possess the greatest antitumor activity and to further elucidate its mechanism of action. METHODS: The transfected B16/F10 cells were irradiated to prevent replication and injected intracranially into C57BL/6 mice (10 mice per group) along with nonirradiated, nontransfected B16/F10 (wild-type) melanoma cells. Sixty percent of mice treated with IL-2 (p <0.001 compared with control) and 10% treated with IL-4 (median survival = 31 days, p <0.001 compared with control) were long term survivors (> 120 days). The median survival for animals treated with GM-CSF was 22 days with no long term survivors (p = 0.01 compared with control). Control animals that received only wild-type cells had a median survival of 18 days (range 15-20 days). Histopathological examination of brains from animals killed at different times showed minimal infiltration of tumor cells in the IL-2 group, moderate infiltration of tumor cells in the IL-4 group, and gross tumor invasion and tissue necrosis in the GM-CSF group. Animals treated with IL-2 showed a strong CD8 T cell-mediated response, whereas IL-4 evoked a prominent eosinophilic infiltrate in the area of the tumor. CONCLUSIONS: High levels of locally expressed IL-2 rather than IL-4 or GM-CSF stimulate a strong immunological cytotoxic antitumor response that leads to significant prolongation of survival in mice challenged with B16/F10 intracranial melanoma tumor cells. Consequently, IL-2 may be a superior candidate for use in paracrine immunotherapy.

Original languageEnglish
JournalNeurosurgical Focus
Volume9
Issue number6
Publication statusPublished - 2000

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Brain Neoplasms
Immunotherapy
Interleukin-2
Colony-Stimulating Factors
Interleukin-4
Central Nervous System Neoplasms
Neoplasms
Cytokines
Survival
Melanoma
Experimental Melanomas
Inbred C57BL Mouse
Survivors
Necrosis
T-Lymphocytes
Brain
Genes

Cite this

Lesniak, M. S., Sampath, P., DiMeco, F., Viglione, M. P., Tyler, B. M., Pardoll, D. M., & Brem, H. (2000). Comparative analysis of paracrine immunotherapy in experimental brain tumors. Neurosurgical Focus, 9(6).

Comparative analysis of paracrine immunotherapy in experimental brain tumors. / Lesniak, M. S.; Sampath, P.; DiMeco, F.; Viglione, M. P.; Tyler, B. M.; Pardoll, D. M.; Brem, H.

In: Neurosurgical Focus, Vol. 9, No. 6, 2000.

Research output: Contribution to journalArticle

Lesniak, MS, Sampath, P, DiMeco, F, Viglione, MP, Tyler, BM, Pardoll, DM & Brem, H 2000, 'Comparative analysis of paracrine immunotherapy in experimental brain tumors.', Neurosurgical Focus, vol. 9, no. 6.
Lesniak MS, Sampath P, DiMeco F, Viglione MP, Tyler BM, Pardoll DM et al. Comparative analysis of paracrine immunotherapy in experimental brain tumors. Neurosurgical Focus. 2000;9(6).
Lesniak, M. S. ; Sampath, P. ; DiMeco, F. ; Viglione, M. P. ; Tyler, B. M. ; Pardoll, D. M. ; Brem, H. / Comparative analysis of paracrine immunotherapy in experimental brain tumors. In: Neurosurgical Focus. 2000 ; Vol. 9, No. 6.
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abstract = "OBJECT: Local delivery of cytokines has been shown to have a potent antitumor activity against a wide range of malignant brain tumors. In this study, the authors examined the efficacy of treating central nervous system (CNS) tumors by transfecting poorly immunogenic B16/F10 melanoma cells with interleukin (IL)-2, IL-4, or granulocytemacrophage-colony stimulating factor (GM-CSF) gene, and using these cells to deliver the cytokine locally at the site of the CNS tumor. The object was to determine which cytokine would possess the greatest antitumor activity and to further elucidate its mechanism of action. METHODS: The transfected B16/F10 cells were irradiated to prevent replication and injected intracranially into C57BL/6 mice (10 mice per group) along with nonirradiated, nontransfected B16/F10 (wild-type) melanoma cells. Sixty percent of mice treated with IL-2 (p <0.001 compared with control) and 10{\%} treated with IL-4 (median survival = 31 days, p <0.001 compared with control) were long term survivors (> 120 days). The median survival for animals treated with GM-CSF was 22 days with no long term survivors (p = 0.01 compared with control). Control animals that received only wild-type cells had a median survival of 18 days (range 15-20 days). Histopathological examination of brains from animals killed at different times showed minimal infiltration of tumor cells in the IL-2 group, moderate infiltration of tumor cells in the IL-4 group, and gross tumor invasion and tissue necrosis in the GM-CSF group. Animals treated with IL-2 showed a strong CD8 T cell-mediated response, whereas IL-4 evoked a prominent eosinophilic infiltrate in the area of the tumor. CONCLUSIONS: High levels of locally expressed IL-2 rather than IL-4 or GM-CSF stimulate a strong immunological cytotoxic antitumor response that leads to significant prolongation of survival in mice challenged with B16/F10 intracranial melanoma tumor cells. Consequently, IL-2 may be a superior candidate for use in paracrine immunotherapy.",
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AU - Lesniak, M. S.

AU - Sampath, P.

AU - DiMeco, F.

AU - Viglione, M. P.

AU - Tyler, B. M.

AU - Pardoll, D. M.

AU - Brem, H.

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N2 - OBJECT: Local delivery of cytokines has been shown to have a potent antitumor activity against a wide range of malignant brain tumors. In this study, the authors examined the efficacy of treating central nervous system (CNS) tumors by transfecting poorly immunogenic B16/F10 melanoma cells with interleukin (IL)-2, IL-4, or granulocytemacrophage-colony stimulating factor (GM-CSF) gene, and using these cells to deliver the cytokine locally at the site of the CNS tumor. The object was to determine which cytokine would possess the greatest antitumor activity and to further elucidate its mechanism of action. METHODS: The transfected B16/F10 cells were irradiated to prevent replication and injected intracranially into C57BL/6 mice (10 mice per group) along with nonirradiated, nontransfected B16/F10 (wild-type) melanoma cells. Sixty percent of mice treated with IL-2 (p <0.001 compared with control) and 10% treated with IL-4 (median survival = 31 days, p <0.001 compared with control) were long term survivors (> 120 days). The median survival for animals treated with GM-CSF was 22 days with no long term survivors (p = 0.01 compared with control). Control animals that received only wild-type cells had a median survival of 18 days (range 15-20 days). Histopathological examination of brains from animals killed at different times showed minimal infiltration of tumor cells in the IL-2 group, moderate infiltration of tumor cells in the IL-4 group, and gross tumor invasion and tissue necrosis in the GM-CSF group. Animals treated with IL-2 showed a strong CD8 T cell-mediated response, whereas IL-4 evoked a prominent eosinophilic infiltrate in the area of the tumor. CONCLUSIONS: High levels of locally expressed IL-2 rather than IL-4 or GM-CSF stimulate a strong immunological cytotoxic antitumor response that leads to significant prolongation of survival in mice challenged with B16/F10 intracranial melanoma tumor cells. Consequently, IL-2 may be a superior candidate for use in paracrine immunotherapy.

AB - OBJECT: Local delivery of cytokines has been shown to have a potent antitumor activity against a wide range of malignant brain tumors. In this study, the authors examined the efficacy of treating central nervous system (CNS) tumors by transfecting poorly immunogenic B16/F10 melanoma cells with interleukin (IL)-2, IL-4, or granulocytemacrophage-colony stimulating factor (GM-CSF) gene, and using these cells to deliver the cytokine locally at the site of the CNS tumor. The object was to determine which cytokine would possess the greatest antitumor activity and to further elucidate its mechanism of action. METHODS: The transfected B16/F10 cells were irradiated to prevent replication and injected intracranially into C57BL/6 mice (10 mice per group) along with nonirradiated, nontransfected B16/F10 (wild-type) melanoma cells. Sixty percent of mice treated with IL-2 (p <0.001 compared with control) and 10% treated with IL-4 (median survival = 31 days, p <0.001 compared with control) were long term survivors (> 120 days). The median survival for animals treated with GM-CSF was 22 days with no long term survivors (p = 0.01 compared with control). Control animals that received only wild-type cells had a median survival of 18 days (range 15-20 days). Histopathological examination of brains from animals killed at different times showed minimal infiltration of tumor cells in the IL-2 group, moderate infiltration of tumor cells in the IL-4 group, and gross tumor invasion and tissue necrosis in the GM-CSF group. Animals treated with IL-2 showed a strong CD8 T cell-mediated response, whereas IL-4 evoked a prominent eosinophilic infiltrate in the area of the tumor. CONCLUSIONS: High levels of locally expressed IL-2 rather than IL-4 or GM-CSF stimulate a strong immunological cytotoxic antitumor response that leads to significant prolongation of survival in mice challenged with B16/F10 intracranial melanoma tumor cells. Consequently, IL-2 may be a superior candidate for use in paracrine immunotherapy.

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