Antigen-presenting cells pulsed with unfractionated tumor-derived peptides are potent tumor vaccines

Smita K. Nair, David Boczkowski, David Snyder, Eli Gilboa

Research output: Contribution to journalArticle

85 Scopus citations

Abstract

Vaccination with peptides isolated from tumor cells circumvents the need for identifying specific tumor rejection antigens and extends the use of active immunotherapy to the majority of cancers where specific tumor antigens have not yet been identified. In this study, we examined the efficacy of tumor vaccines composed of unfractionated tumor peptides presented by antigen-presenting cells (APC) to induce cytotoxic T lymphocyte (CTL) responses and tumor immunity. RMA-S cells pulsed with peptides isolated from ovalbumin (OVA)-expressing tumor cells were highly effective at inducing primary, OVA-specific CTL responses in vitro and priming CTL responses in vivo. In addition, tumor peptide-pulsed RMA-S cells induced protective immunity in mice when challenged with OVA-expressing tumor cells. To enhance the clinical relevance of these studies, cells pulsed with tumor peptides were evaluated in the poorly immunogenic, B16/F10.9 melanoma post-surgical metastasis model. Treatment of tumor-bearing mice with peptide-pulsed RMA-S cells or with adherent splenocytes (enriched for professional APC) caused a significant reduction in lung metastases. The antimetastatic effect of peptide-pulsed splenocytes could be further enhanced by pretreating the cells with antisense oligonucleotides directed against the TAP-2 gene which was previously shown to increase the density of specific peptide/MHC class I complexes and thereby improve the APC function of the treated cells. This study suggests that APC loaded with unfractionated peptides derived from poorly immunogenic, highly metastatic tumor cells may represent a potent form of tumor vaccine.

Original languageEnglish (US)
Pages (from-to)589-597
Number of pages9
JournalEuropean Journal of Immunology
Volume27
Issue number3
DOIs
StatePublished - Mar 20 1997
Externally publishedYes

Keywords

  • Antigen-presenting cell
  • Cytotoxic T lymphocyte
  • Peptide extract
  • RMA-S cell
  • Tumor vaccine

ASJC Scopus subject areas

  • Immunology

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