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

Tumor associated lymphocites (TAL) isolated from malignant ascites cultured in media containing interleukin-2 show antitumor responses. These antitumo r responses are mediated by cytotoxic T lymphocytes (CTL) which recognize a ntigen in the context of MHC molecules using T cell receptors. CD8+ CTL rec ognize peptide epitopes processed fr om cellular proteins in the context of MHC class I molecules. These peptides have a restricted length of 8-11 ami no 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 sou rce of antigenic peptides recognized by a number of these CTL-TAL. This ind icated that FBP peptides are antigenic in vivo for ovarian and bi east 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 d onors isolated by the CD14 method to ovarian and breast CTL-TAL. Stimulatio n 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 re sponder population consisted of cells expressing TCR V beta 9, V beta 13, a nd V beta 17 families based on the increase in the percentages of these fam ilies in DC-E39 versus DC-NP stimulated TAL. Characterization of immunogeni c tumor antigens and of cytokine requirements for induction of functional a ntitumor effectors may be important for future cancer vaccine developments.