Identification of HLA-A24 epitope peptides of carcinoembryonic antigen which induce tumor-reactive cytotoxic T lymphocyte

✍ Scribed by Ikuei Nukaya; Masazumi Yasumoto; Tomoko Iwasaki; Mitsuko Ideno; Alessandro Sette; Esteban Celis; Kazutoh Takesako; Ikunoshin Kato

• Publisher: John Wiley and Sons
• Year: 1999
• Tongue: French
• Weight: 135 KB
• Volume: 80
• Category: Article
• ISSN: 0020-7136
• DOI: 10.1002/(sici)1097-0215(19990105)80:1<92::aid-ijc18>3.0.co;2-m

✦ Synopsis

Carcinoembryonic antigen (CEA), which is expressed in several cancer types, 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 peripheral blood mononuclear cells (PBMC) of a healthy donor and autologous peptide-pulsed dendritic cells as antigenpresenting cells. This approach 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 of the 2 CTL lines was examined using several tumor cell lines of various 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-A24 ؉ patients with tumors that express CEA.