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Identification of HLA‐A24 epitope peptides of carcinoembryonic antigen which induce tumor‐reactive cytotoxic T lymphocyte
Author(s) -
Nukaya Ikuei,
Yasumoto Masazumi,
Iwasaki Tomoko,
Ideno Mitsuko,
Sette Alessandro,
Celis Esteban,
Takesako Kazutoh,
Kato Ikunoshin
Publication year - 1999
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/(sici)1097-0215(19990105)80:1<92::aid-ijc18>3.0.co;2-m
Subject(s) - cytotoxic t cell , ctl* , epitope , antigen , carcinoembryonic antigen , immunology , major histocompatibility complex , immunotherapy , human leukocyte antigen , cd8 , monoclonal antibody , biology , peripheral blood mononuclear cell , tumor antigen , antibody , immune system , cancer , in vitro , biochemistry , genetics
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 antigen‐presenting 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. Int. J. Cancer 80:92–97, 1999. © 1999 Wiley‐Liss, Inc.