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Subcutaneous vaccination with irradiated, cytokine-producing tumor cells stimulates CD8+ cell-mediated immunity against tumors located in the "immunologically privileged" central nervous system.

Publication ,  Journal Article
Sampson, JH; Archer, GE; Ashley, DM; Fuchs, HE; Hale, LP; Dranoff, G; Bigner, DD
Published in: Proc Natl Acad Sci U S A
September 17, 1996

Vaccination with cytokine-producing tumor cells generates potent immune responses against tumors outside the central nervous system (CNS). The CNS, however, is a barrier to allograft and xenograft rejection, and established tumors within the CNS have failed to respond to other forms of systemic immunotherapy. To determine what barriers the "immunologically privileged" CNS would pose to cytokine-assisted tumor vaccines and what cytokines would be most efficacious against tumors within the CNS, we irradiated B16 murine melanoma cells producing murine interleukin 2 (IL-2), IL-3, IL-4, IL-6, gamma-interferon, or granulocyte-macrophage colony stimulating factor (GM-CSF) and used these cells as subcutaneous vaccines against tumors within the brain. Under conditions where untransfected B16 cells had no effect, cells producing IL-3, IL-6, or GM-CSF increased the survival of mice challenged with viable B16 cells in the brain. Vaccination with B16 cells producing IL-4 or gamma-interferon had no effect, and vaccination with B16 cells producing IL-2 decreased survival time. GM-CSF-producing vaccines were also able to increase survival in mice with pre-established tumors. The response elicited by GM-CSF-producing vaccines was found to be specific to tumor type and to be abrogated by depletion of CD8+ cells. Unlike the immunity generated against subcutaneous tumors by GM-CSF, however, the effector responses generated against tumors in the CNS were not dependent on CD4+ cells. These data suggest that cytokine-producing tumor cells are very potent stimulators of immunity against tumors within the CNS, but effector responses in the CNS may be different from those obtained against subcutaneous tumors.

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Published In

Proc Natl Acad Sci U S A

DOI

ISSN

0027-8424

Publication Date

September 17, 1996

Volume

93

Issue

19

Start / End Page

10399 / 10404

Location

United States

Related Subject Headings

  • Transfection
  • T-Lymphocytes
  • Spleen
  • Recombinant Proteins
  • Mice, Inbred C57BL
  • Mice
  • Melanoma, Experimental
  • Lung Neoplasms
  • Killer Cells, Natural
  • Interleukin-4
 

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Sampson, J. H., Archer, G. E., Ashley, D. M., Fuchs, H. E., Hale, L. P., Dranoff, G., & Bigner, D. D. (1996). Subcutaneous vaccination with irradiated, cytokine-producing tumor cells stimulates CD8+ cell-mediated immunity against tumors located in the "immunologically privileged" central nervous system. Proc Natl Acad Sci U S A, 93(19), 10399–10404. https://doi.org/10.1073/pnas.93.19.10399
Sampson, J. H., G. E. Archer, D. M. Ashley, H. E. Fuchs, L. P. Hale, G. Dranoff, and D. D. Bigner. “Subcutaneous vaccination with irradiated, cytokine-producing tumor cells stimulates CD8+ cell-mediated immunity against tumors located in the "immunologically privileged" central nervous system.Proc Natl Acad Sci U S A 93, no. 19 (September 17, 1996): 10399–404. https://doi.org/10.1073/pnas.93.19.10399.
Sampson, J. H., et al. “Subcutaneous vaccination with irradiated, cytokine-producing tumor cells stimulates CD8+ cell-mediated immunity against tumors located in the "immunologically privileged" central nervous system.Proc Natl Acad Sci U S A, vol. 93, no. 19, Sept. 1996, pp. 10399–404. Pubmed, doi:10.1073/pnas.93.19.10399.
Sampson JH, Archer GE, Ashley DM, Fuchs HE, Hale LP, Dranoff G, Bigner DD. Subcutaneous vaccination with irradiated, cytokine-producing tumor cells stimulates CD8+ cell-mediated immunity against tumors located in the "immunologically privileged" central nervous system. Proc Natl Acad Sci U S A. 1996 Sep 17;93(19):10399–10404.
Journal cover image

Published In

Proc Natl Acad Sci U S A

DOI

ISSN

0027-8424

Publication Date

September 17, 1996

Volume

93

Issue

19

Start / End Page

10399 / 10404

Location

United States

Related Subject Headings

  • Transfection
  • T-Lymphocytes
  • Spleen
  • Recombinant Proteins
  • Mice, Inbred C57BL
  • Mice
  • Melanoma, Experimental
  • Lung Neoplasms
  • Killer Cells, Natural
  • Interleukin-4