Acaid terminates systemic protective anti-tumor immunity induced by b7.1 + il-12 transfected tumor cells

B. R. Ksander, T. Uno, D. C. Geer, E. R. Podack, P. W. Chen

Research output: Contribution to journalArticle

Abstract

Purpose Mice immunized with tumor cells transfected with B7.1 and IL-12 genes are protected from a second subcutaneous challenge of untransfected tumor cells. The following experiments were performed to determine if ACAJD can be induced in presensitized mice which already possess primed T cells capable of eliminating tumor cells from non-privileged sites. Methods DBA/2 mice were immunized by a subcutaneous injection of B7.1 + IL-12 P815 cells. Four weeks later, tumor growth and survival was determined following inoculation of untransfected P815 tumor cells into either the: (i) anterior chamber, (u) contralaleral flank, or (iu) simultaneously into the eye and flank. Tumor specific cytotoxic T cells were assayed using a standard chromium release assay. Contribution of CD4 and CDS T cells in protective immunity was determined by in vivo antibody depletion experiments. Results Immunized mice generated tumor-specific CD8+ cytotoxic T cells and CD4+ helper T cells which eliminated up to 2 x 10-4 untransfected tumor cells inoculated into the subcutaneous tissues of the contralateral flank. By contrast, immunized mice were unable to eliminate as few as 2 x 10-4 tumor cells inoculated into the anterior chamber. In addition, immunized mice receiving simultaneous eye and flank inoculations were unable to eliminate tumor cells from either site. Conclusions Tumor cells that express B7.1 and IL-12 costimulatory signals induce specific cytotoxic T cells and helper T cells that eliminate tumor cells from non-immune privileged sites. By contrast, tumors within the privileged anterior chamber terminate systemic protective immunity. Our results imply that tumor-cell vaccines, which successfully eliminate tumors from non-privileged sites. will be ineffective if tumor cells subsequently migrate to an immune privilege site.

Original languageEnglish (US)
Pages (from-to)S492
JournalInvestigative Ophthalmology and Visual Science
Volume38
Issue number4
StatePublished - Dec 1 1997

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

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