Dendritic cell-based immunotherapy for colon cancer using an HLA-A＊0201-restricted cytotoxic T-lymphocyte epitope from tumor-associated antigen 90K

• Published in: 中国免疫学杂志：英文版 2013, Vol.10 (3), p.275-282
• Main Author: Ji Hee Lee Myong-Suk Park Jun-Eul Hwang Sang-Hee Cho Woo-Kyun Bae Hyun-Jeong Shim Dae-Eun Kim Ik-Joo Chung
• Format: Article
• Language: English
• Subjects: HLA-A; 免疫治疗; 基础; 抗原; 树突状细胞; 细胞毒性T淋巴细胞; 结肠癌; 肿瘤组织
• ISSN: 1672-7681; 2042-0226

Tumor-associated antigen 90K is implicated in cell-cell and cell-extracellular matrix adhesion through its interaction with galectin-3 and integrin-β 1 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 （90K3s1, 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 Thl. 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＊O2Ol-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 immunotherapv treatment of colon cancer.