TY - JOUR
T1 - Identification of HLA-A24 epitope peptides of carcinoembryonic antigen which induce tumor-reactive cytotoxic T lymphocyte
AU - Nukaya, I.
AU - Yasumoto, M.
AU - Iwasaki, T.
AU - Ideno, M.
AU - Sette, A.
AU - Celis, E.
AU - Takesako, K.
AU - Kato, I.
PY - 1999/1/5
Y1 - 1999/1/5
N2 - 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.
AB - 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.
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U2 - 10.1002/(SICI)1097-0215(19990105)80:1<92::AID-IJC18>3.0.CO;2-M
DO - 10.1002/(SICI)1097-0215(19990105)80:1<92::AID-IJC18>3.0.CO;2-M
M3 - Article
C2 - 9935237
AN - SCOPUS:0033524378
SN - 0020-7136
VL - 80
SP - 92
EP - 97
JO - International Journal of Cancer
JF - International Journal of Cancer
IS - 1
ER -