Vaccination with irradiated tumor cells engineered to secrete murine granulocyte-macrophage colony-stimulating factor stimulates potent, specific, and long-lasting anti-tumor immunity

Glenn Dranoff, Elizabeth Jaffee, Audrey J Lazenby, Paul Golumbek, Hyam Levitsky, Katja Brose, Valerie Jackson, Hirofumi Hamada, Drew Pardoll, Richard C. Mulligan

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Abstract

To compare the ability of different cytokines and other molecules to enhance the immunogenicity of tumor cells, we generated 10 retroviruses encoding potential immunomodulators and studied the vaccination properties of murine tumor cells transduced by the viruses. Using a B16 melanoma model, in which irradiated tumor cells alone do not stimulate significant anti-tumor immunity, we found that irradiated tumor cells expressing murine granulocyte-macrophage colony-stimulating factor (GM-CSF) stimulated potent, long-lasting, and specific anti-tumor immunity, requiring both CD4+ and CD8+ cells. Irradiated cells expressing interleukins 4 and 6 also stimulated detectable, but weaker, activity. In contrast to the B16 system, we found that in a number of other tumor models, the levels of anti-tumor immunity reported previously in cytokine gene transfer studies involving live, transduced cells could be achieved through the use of irradiated cells alone. Nevertheless, manipulation of the vaccine or challenge doses made it possible to demonstrate the activity of murine GM-CSF in those systems as well. Overall, our results have important implications for the clinical use of genetically modified tumor cells as therapeutic cancer vaccines.

Original languageEnglish (US)
Pages (from-to)3539-3543
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume90
Issue number8
DOIs
StatePublished - Apr 15 1993

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Granulocyte-Macrophage Colony-Stimulating Factor
Immunity
Vaccination
Neoplasms
Cytokines
Experimental Melanomas
Cancer Vaccines
Immunologic Factors
Retroviridae
Interleukin-4
Interleukin-6
Vaccines
Viruses

Keywords

  • Gene transfer
  • Tumor immunology

ASJC Scopus subject areas

  • General

Cite this

Vaccination with irradiated tumor cells engineered to secrete murine granulocyte-macrophage colony-stimulating factor stimulates potent, specific, and long-lasting anti-tumor immunity. / Dranoff, Glenn; Jaffee, Elizabeth; Lazenby, Audrey J; Golumbek, Paul; Levitsky, Hyam; Brose, Katja; Jackson, Valerie; Hamada, Hirofumi; Pardoll, Drew; Mulligan, Richard C.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 90, No. 8, 15.04.1993, p. 3539-3543.

Research output: Contribution to journalArticle

Dranoff, Glenn ; Jaffee, Elizabeth ; Lazenby, Audrey J ; Golumbek, Paul ; Levitsky, Hyam ; Brose, Katja ; Jackson, Valerie ; Hamada, Hirofumi ; Pardoll, Drew ; Mulligan, Richard C. / Vaccination with irradiated tumor cells engineered to secrete murine granulocyte-macrophage colony-stimulating factor stimulates potent, specific, and long-lasting anti-tumor immunity. In: Proceedings of the National Academy of Sciences of the United States of America. 1993 ; Vol. 90, No. 8. pp. 3539-3543.
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