title: Dendritic cell-based immunotherapy for colon cancer using an HLA-A*0201-restricted cytotoxic T-lymphocyte epitope from tumor-associated antigen 90K.
abstract: Tumor-associated antigen 90K is implicated in cell-cell and cell-extracellular matrix adhesion through its interaction with galectin-3 and integrin-β1 and is highly expressed in malignant tissues, making it a novel target for the development of new immunotherapies. We investigated a potential immunotherapy treatment for colon cancer using 90K-specific cytotoxic T lymphocytes induced by autologous dendritic cells and pulsed with 90K peptides. We selected three peptides (90K351, 90K5 and 90K523) that bind to HLA-A*0201 molecules on the basis of their binding affinity, as determined by a peptide-T2 binding assay. Dendritic cells pulsed with 90K peptides resulted in the efficient generation of mature dendritic cells and exhibited enhanced T-cell stimulation and polarization of naive T cells toward Th1. Dendritic cells pulsed with 90K peptides generated potent cytotoxic T-lymphocytes that lysed T2 cells loaded with each 90K peptide, and 90K(+)/HLA-A2(+) colon cancer cell lines, including HCT116 and SW480, in a dose-dependent and HLA-A*0201-restricted manner. No killing was observed in 90K(+)/HLA-A2(-) DLD1 or 90K(-)/HLA-A2(-) K562 cells. Therefore, we believe that cytotoxic T-lymphocytes stimulated by 90K peptide-pulsed dendritic cells naturally recognize the 90K peptide presented by colon cancer cells in the context of HLA-A2, and kill 90K-positive tumor cells. Dendritic cells pulsed with 90K peptides led to the induction of granzyme B and perforin positive CD8(+) T cells against HCT116 and SW480 cells, but not DLD1 cells. In conclusion, 90K-specific cytotoxic T lymphocytes, generated by stimulating T cells with 90K peptide-pulsed dendritic cells, could be useful effector cells for the immunotherapy treatment of colon cancer.
authors.affiliation: Department of Hematology-Oncology, Chonnam National University Medical School, Gwangju, Korea.
authors.forename: Ji
authors.initials: J
authors.lastname: Hee Lee
authors.forename: Myong-Suk
authors.initials: MS
authors.lastname: Park
authors.forename: Jun-Eul
authors.initials: JE
authors.lastname: Hwang
authors.forename: Sang-Hee
authors.initials: SH
authors.lastname: Cho
authors.forename: Woo-Kyun
authors.initials: WK
authors.lastname: Bae
authors.forename: Hyun-Jeong
authors.initials: HJ
authors.lastname: Shim
authors.forename: Dae-Eun
authors.initials: DE
authors.lastname: Kim
authors.forename: Ik-Joo
authors.initials: IJ
authors.lastname: Chung
mesh_terms: D000595:Amino Acid Sequence; D000951:Antigens, Neoplasm / Q000737:chemistry / Q000276:immunology*; D014408:Biomarkers, Tumor / Q000737:chemistry / Q000276:immunology*; D002352:Carrier Proteins / Q000737:chemistry / Q000276:immunology*; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000276:immunology / Q000628:therapy*; D003713:Dendritic Cells / Q000276:immunology*; D000939:Epitopes / Q000737:chemistry / Q000276:immunology*; D006023:Glycoproteins / Q000737:chemistry / Q000276:immunology*; D015789:HLA-A2 Antigen / Q000276:immunology*; D006801:Humans; D007167:Immunotherapy; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry; D011485:Protein Binding / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D016326:Extracellular Matrix Proteins
chemical_list: D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D002352:Carrier Proteins; D000939:Epitopes; D006023:Glycoproteins; D015789:HLA-A2 Antigen; D010455:Peptides; C435939:HLA-A*02:01 antigen; C081856:LGALS3BP protein, human; D016326:Extracellular Matrix Proteins