ANTIGEN-PRESENTING CELLS PULSED WITH UNFRACTIONATED TUMOR-DERIVED PEPTIDES ARE POTENT TUMOR VACCINES

Vaccination with peptides isolated from tumor cells circumvents the ne ed for identifying specific tumor rejection antigens and extends the u se of active immunotherapy to the majority of cancers where specific t umor antigens have not yet been identified. In this study, we examined the efficacy of tumor vaccines composed of unfractionated tumor pepti des 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 hi ghly effective at inducing primary, OVA-specific CTL responses in vitr o 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 poorl y immunogenic, B16/F10.9 melanoma post-surgical metastasis model. Trea tment of tumor-bearing mice with peptide-pulsed RMA-S cells or with ad herent splenocytes (enriched for professional APC) caused a significan t reduction in lung metastases. The antimetastatic effect of peptide-p ulsed splenocytes could be further enhanced by pretreating the cells w ith antisense oligonucleotides directed against the TAP-2 gene which w as previously shown to increase the density of specific peptide/MHC cl ass I complexes and thereby improve the APC function of the treated ce lls (Nair et el., J. Immunol. 1996. 156: 1772). This study suggests th at APC loaded with unfractionated peptides derived from poorly immunog enic, highly metastatic tumor cells may represent a potent form of tum or vaccine.