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Identification of HER2/neu-derived peptide epitopes recognized by gastric cancer-specific cytotoxic T lymphocytes. 1998

K Kono, and Y Rongcun, and J Charo, and F Ichihara, and E Celis, and A Sette, and E Appella, and T Sekikawa, and Y Matsumoto, and R Kiessling
First Department of Surgery, Yamanashi Medical University, Japan. kojikono@res.yamanashi-med.ac.jp

We have derived HLA-A2.1-restricted, gastric cancer-specific cytotoxic T lymphocyte (CTL) lines by repetitive in vitro stimulation of tumor-associated lymphocytes (TAL) with autologous tumor cells. The HER2/neu specificity of these gastric cancer-specific CTLs was demonstrated using HER2/neu-transfected cell lines and HER2/neu-expressing tumors, and with a set of HER2/neu-derived peptide epitopes. Gastric cancer-specific CTLs specifically lysed autologous and allogeneic HLA-A2.1+, HER2/neu+ gastric cancer cells, HER2/neu-transfected C1R/A2 cell lines (HLA-A2.1+, HER2+) and HLA-A2.1-transfected SW626 tumor cell lines (HLA-A2.1+, HER2+). This recognition could be inhibited by anti-HLA-A2 antibody or by cold target HER2/neu-transfected C1R/A2 cells. Our results demonstrate that the HER2/neu-encoded HLA-A2.1-associated epitopes recognized by CTLs are presented as naturally processed peptides on gastric cancer lines. Furthermore, 3 of 19 tested HER2/neu-derived peptide epitopes [HER2(9(106)), HER2(9(369)), HER2(9(689))], which all bound HLA-A2.1 with high (IC50 < 50 nM) affinity, were able to sensitize HLA-A2+ C1R/A2 cells to be recognized by the gastric cancer-specific CTLs, demonstrating the immunodominance of these epitopes. In conclusion, our findings implicate HER2/neu-derived epitopes as potential candidates for novel immunotherapy and vaccine strategies against gastric cancer.

UI MeSH Term Description Entries
D008213 Lymphocyte Activation Morphologic alteration of small B LYMPHOCYTES or T LYMPHOCYTES in culture into large blast-like cells able to synthesize DNA and RNA and to divide mitotically. It is induced by INTERLEUKINS; MITOGENS such as PHYTOHEMAGGLUTININS, and by specific ANTIGENS. It may also occur in vivo as in GRAFT REJECTION. Blast Transformation,Blastogenesis,Lymphoblast Transformation,Lymphocyte Stimulation,Lymphocyte Transformation,Transformation, Blast,Transformation, Lymphoblast,Transformation, Lymphocyte,Activation, Lymphocyte,Stimulation, Lymphocyte
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D012680 Sensitivity and Specificity Binary classification measures to assess test results. Sensitivity or recall rate is the proportion of true positives. Specificity is the probability of correctly determining the absence of a condition. (From Last, Dictionary of Epidemiology, 2d ed) Specificity,Sensitivity,Specificity and Sensitivity
D013274 Stomach Neoplasms Tumors or cancer of the STOMACH. Cancer of Stomach,Gastric Cancer,Gastric Neoplasms,Stomach Cancer,Cancer of the Stomach,Gastric Cancer, Familial Diffuse,Neoplasms, Gastric,Neoplasms, Stomach,Cancer, Gastric,Cancer, Stomach,Cancers, Gastric,Cancers, Stomach,Gastric Cancers,Gastric Neoplasm,Neoplasm, Gastric,Neoplasm, Stomach,Stomach Cancers,Stomach Neoplasm
D013602 T-Lymphocytes, Cytotoxic Immunized T-lymphocytes which can directly destroy appropriate target cells. These cytotoxic lymphocytes may be generated in vitro in mixed lymphocyte cultures (MLC), in vivo during a graft-versus-host (GVH) reaction, or after immunization with an allograft, tumor cell or virally transformed or chemically modified target cell. The lytic phenomenon is sometimes referred to as cell-mediated lympholysis (CML). These CD8-positive cells are distinct from NATURAL KILLER CELLS and NATURAL KILLER T-CELLS. There are two effector phenotypes: TC1 and TC2. Cell-Mediated Lympholytic Cells,Cytotoxic T Cells,Cytotoxic T Lymphocyte,Cytotoxic T-Lymphocytes,TC1 Cell,TC1 Cells,TC2 Cell,TC2 Cells,Cell Mediated Lympholytic Cells,Cell, Cell-Mediated Lympholytic,Cell, TC1,Cell, TC2,Cell-Mediated Lympholytic Cell,Cytotoxic T Cell,Cytotoxic T Lymphocytes,Cytotoxic T-Lymphocyte,Lymphocyte, Cytotoxic T,Lympholytic Cell, Cell-Mediated,Lympholytic Cells, Cell-Mediated,T Cell, Cytotoxic,T Lymphocyte, Cytotoxic,T Lymphocytes, Cytotoxic,T-Lymphocyte, Cytotoxic
D014162 Transfection The uptake of naked or purified DNA by CELLS, usually meaning the process as it occurs in eukaryotic cells. It is analogous to bacterial transformation (TRANSFORMATION, BACTERIAL) and both are routinely employed in GENE TRANSFER TECHNIQUES. Transfections
D014407 Tumor Cells, Cultured Cells grown in vitro from neoplastic tissue. If they can be established as a TUMOR CELL LINE, they can be propagated in cell culture indefinitely. Cultured Tumor Cells,Neoplastic Cells, Cultured,Cultured Neoplastic Cells,Cell, Cultured Neoplastic,Cell, Cultured Tumor,Cells, Cultured Neoplastic,Cells, Cultured Tumor,Cultured Neoplastic Cell,Cultured Tumor Cell,Neoplastic Cell, Cultured,Tumor Cell, Cultured
D015789 HLA-A2 Antigen A specific HLA-A surface antigen subtype. Members of this subtype contain alpha chains that are encoded by the HLA-A*02 allele family. HLA Class I Histocompatibility Antigen, A-2 alpha Chain,HLA-A2,Antigen, HLA-A2,HLA A2 Antigen,HLA Class I Histocompatibility Antigen, A 2 alpha Chain
D016056 Immunodominant Epitopes Subunits of the antigenic determinant that are most easily recognized by the immune system and thus most influence the specificity of the induced antibody. Antigenic Determinants, Immunodominant,Antigens, Immunodominant,Epitopes, Immunodominant,Immunodominant Determinant,Immunodominant Domain,Immunodominant Epitope,Immunodominant Region,Immunodominant Site,Immunodominant Determinants,Immunodominant Domains,Immunodominant Regions,Immunodominant Sites,Determinant, Immunodominant,Determinants, Immunodominant,Determinants, Immunodominant Antigenic,Domain, Immunodominant,Domains, Immunodominant,Epitope, Immunodominant,Immunodominant Antigenic Determinants,Immunodominant Antigens,Region, Immunodominant,Regions, Immunodominant,Site, Immunodominant,Sites, Immunodominant
D016246 Lymphocytes, Tumor-Infiltrating Lymphocytes that show specificity for autologous tumor cells. Ex vivo isolation and culturing of TIL with interleukin-2, followed by reinfusion into the patient, is one form of adoptive immunotherapy of cancer. Tumor Infiltrating Lymphocyte,Tumor-Derived Activated Cell,Tumor-Derived Activated Cells,Tumor-Infiltrating Lymphocyte,Tumor-Infiltrating Lymphocytes,Activated Cell, Tumor-Derived,Activated Cells, Tumor-Derived,Infiltrating Lymphocyte, Tumor,Infiltrating Lymphocytes, Tumor,Lymphocyte, Tumor Infiltrating,Lymphocyte, Tumor-Infiltrating,Lymphocytes, Tumor Infiltrating,Tumor Derived Activated Cell,Tumor Derived Activated Cells,Tumor Infiltrating Lymphocytes

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