Folate binding protein peptide 191-199 presented on dendritic cells can stimulate CTL from ovarian and breast cancer patients

Abstract

Tumor associated lymphocytes (TAL) isolated from malignant ascites cultured in media containing interleukin-2 show antitumor responses. These antitumor responses are mediated by cytotoxic T lymphocytes (CTL) which recognize antigen in the context of MHC molecules using T cell receptors. CD8+ CTL recognize peptide epitopes processed from cellular proteins in the context of MHC class I molecules. These peptides have a restricted length of 8-11 amino acids. The folate binding protein (FBP) is overexpressed in over 90% of ovarian and 20-50% of breast cancers. We recently found that FBP is the source of antigenic peptides recognized by a number of these CTL-TAL. This indicated that FBP peptides are antigenic in vivo for ovarian and breast CTL-TAL. To define FBP immunogenicity, a peptide defining the epitope E39 (FBP, 191-199) was presented by PMBC derived dendritic cells (DC) from healthy donors isolated by the CD14 method to ovarian and breast CTL-TAL. Stimulation of ovarian and breast CTL-TAL by E39 pulsed DC (DC-E39), in the presence of IL-2, rapidly enhanced or induced E39 specific CTL activity. This E39-responder population consisted of cells expressing TCR V beta 9, V beta 13, and V beta 17 families, based on the increase in the percentages of these families in DC-E39 versus DC-NP stimulated TAL. Characterization of immunogenic tumor antigens and of cytokine requirements for induction of functional antitumor effectors may be important for future cancer vaccine developments.