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


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2013-05

AUTHORS

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

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. More... »

PAGES

cmi201274

References to SciGraph publications

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/cmi.2012.74

DOI

http://dx.doi.org/10.1038/cmi.2012.74

DIMENSIONS

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PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/23524651


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