IDENTIFICATION OF HLA-A24 EPITOPE PEPTIDES OF CARCINOEMBRYONIC ANTIGEN WHICH INDUCE TUMOR-REACTIVE CYTOTOXIC T-LYMPHOCYTE

Carcinoembryonic antigen (CEA), which is expressed in several cancer t ypes, is a potential target for specific immunotherapy. HLA-A24 is the most frequent allele among Japanese and is also frequently present in Asians and Caucasians. We tested CEA-encoded HLA-A24 binding peptides for their capacity to elicit anti-tumor cytotoxic T lymphocytes (CTL) in vitro. For this purpose, we used CD8(+) T lymphocytes from periphe ral blood mononuclear cells (PBMC) of a healthy donor and autologous p eptide-pulsed dendritic cells as antigen-presenting cells. This approa ch enabled us to identify 2 peptides, QYSWFVNGTF and TYACFVSNL, which were capable of eliciting CTL lines that lysed tumor cells expressing HLA-A24 and CEA, The cytotoxicity to tumor cells by the CTL lines was antigen-specific since it was inhibited by peptide-pulsed cold target cells as well as by anti-class I major histocompatibility complex (MHC ) and anti-CD3 monoclonal antibodies (MAbs). The antigen specificity o f the 2 CTL lines was examined using several tumor cell lines of vario us origins and for their peptide-dose responses. The identification of these novel CEA epitopes for CTL offers the opportunity to design and develop epitope-based immunotherapeutic approaches for treating HLA-A 24(+) patients with tumors that express CEA. (C) 1999 Wiley-Liss, Inc.