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

Cellular & Molecular Immunology volume 10, pages 275–282 (2013)Cite this article

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.

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Acknowledgements

This study was financially supported by a grant from the National R&D Program for Cancer Control, Ministry for Health, Welfare and Family affairs, Republic of Korea (0720570) and the National Research Foundation of Korea (2012-0002351).

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Authors and Affiliations

  1. Department of Hematology-Oncology, Chonnam National University Medical School, Gwangju, Korea

    Ji Hee Lee, Myong-Suk Park, Jun-Eul Hwang, Sang-Hee Cho, Woo-Kyun Bae, Hyun-Jeong Shim, Dae-Eun Kim & Ik-Joo Chung

  2. The Brain Korea 21 Project, Center for Biomedical Human Resources at Chonnam National University, Gwangju, Korea

    Ik-Joo Chung

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  1. Ji Hee Lee
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Hee Lee, J., Park, MS., Hwang, JE. et al. Dendritic cell-based immunotherapy for colon cancer using an HLA-A*0201-restricted cytotoxic T-lymphocyte epitope from tumor-associated antigen 90K. Cell Mol Immunol 10, 275–282 (2013). https://doi.org/10.1038/cmi.2012.74

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