Systemic and local paracrine cytokine therapies using transduced tumor cells are synergistic in treating intracranial tumors

R. C. Thompson, Andrew Mark Pardoll, Elizabeth Jaffee, M. G. Ewend, M. C. Thomas, Betty Mae Tyler, Henry Brem

Research output: Contribution to journalArticle

Abstract

Development of an effective immunotherapeutic approach for treatment of CNS tumors must take into account the unique anatomic and immunologic features of the brain. We explored the antitumor immune response in the brain elicited by nonreplicating melanoma cells genetically engineered to produce either granulocyte-macrophage colony-stimulating factor (GM-CSF) or interleukin-2 (IL-2) in a paracrine fashion. Using a new model of intracranial melanoma in C57BL/6 mice, the cytokine-producing cells were given either as a subcutaneous vaccine to induce systemic anti-tumor immunity or as a direct injection into the brain as local immunotherapy. We found that GM-CSF-transduced cells, as a subcutaneous vaccine but not as an intracranial injection, afforded some protection from intracranial challenge with the wild-type tumor. In contrast, direct intracranial injection of tumor cells secreting IL-2 was protective whereas flank vaccination with IL-2 transductants was not. Combination therapy with both the subcutaneous GM- CSF-transductants as a vaccine and local administration of IL-2-transductants in the brain achieved a synergistic response. These findings provide a basis for the application of paracrine cytokine delivery to brain cancer therapy both as a systemic vaccine and via local administration. The demonstration of synergy between paracrine cytokine therapies holds promise as a novel therapy for brain tumors.

Original languageEnglish (US)
Pages (from-to)405-413
Number of pages9
JournalJournal of Immunotherapy
Volume19
Issue number6
DOIs
StatePublished - 1996

Fingerprint

Interleukin-2
Cytokines
Vaccines
Granulocyte-Macrophage Colony-Stimulating Factor
Brain
Neoplasms
Brain Neoplasms
Injections
Melanoma
Therapeutics
Inbred C57BL Mouse
Immunotherapy
Immunity
Vaccination

Keywords

  • Brain tumor
  • CNS
  • Cytokine
  • GM-CSF
  • IL-2

ASJC Scopus subject areas

  • Cancer Research
  • Pharmacology
  • Immunology

Cite this

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abstract = "Development of an effective immunotherapeutic approach for treatment of CNS tumors must take into account the unique anatomic and immunologic features of the brain. We explored the antitumor immune response in the brain elicited by nonreplicating melanoma cells genetically engineered to produce either granulocyte-macrophage colony-stimulating factor (GM-CSF) or interleukin-2 (IL-2) in a paracrine fashion. Using a new model of intracranial melanoma in C57BL/6 mice, the cytokine-producing cells were given either as a subcutaneous vaccine to induce systemic anti-tumor immunity or as a direct injection into the brain as local immunotherapy. We found that GM-CSF-transduced cells, as a subcutaneous vaccine but not as an intracranial injection, afforded some protection from intracranial challenge with the wild-type tumor. In contrast, direct intracranial injection of tumor cells secreting IL-2 was protective whereas flank vaccination with IL-2 transductants was not. Combination therapy with both the subcutaneous GM- CSF-transductants as a vaccine and local administration of IL-2-transductants in the brain achieved a synergistic response. These findings provide a basis for the application of paracrine cytokine delivery to brain cancer therapy both as a systemic vaccine and via local administration. The demonstration of synergy between paracrine cytokine therapies holds promise as a novel therapy for brain tumors.",
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AU - Pardoll, Andrew Mark

AU - Jaffee, Elizabeth

AU - Ewend, M. G.

AU - Thomas, M. C.

AU - Tyler, Betty Mae

AU - Brem, Henry

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