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Title 

Identification of novel HLA-A*0201-restricted epitopes from anterior gradient-2 as a tumor-associated antigen against colorectal cancer

 

대장암 마커 AGR2의 신규 epitope HLA-A*0201 확인

Authors 

H J LeeC Y HongC J JinM H KimY K LeeT N Nguyen-PhamH LeeByoung Chul ParkI J ChungH J KimJ J Lee

Publisher 

Chinese Society of Immunology

Issue Date 

2012

Citation 

Cellular & Molecular Immunology

Keywords 

AGR2colorectal cancerdendritic celltumor-associated antigen

Abstract 

Anterior gradient-2 (AGR2) promotes tumor growth, cell migration and cellular transformation and its enhanced expression is almost completely restricted to malignant tissues, thus making AGR2 an interesting target for the development of immunotherapeutic strategies. We investigated whether the AGR2 molecule comprises human leukocyte antigen (HLA)-A0201-binding epitopes recognized by human cytotoxic T lymphocytes (CTLs), which could be targeted in dendritic cell (DC)-based cancer immunotherapy against colorectal cancer (CRC). We reviewed the sequence of AGR2 for peptides that could potentially bind to HLA-A0201 with the aid of a computer-based program. Five candidate peptides with different binding scores were synthesized and tested. These peptides were then assessed for their immunogenicity to elicit specific immune responses mediated by CTLs in vitro by means of enzyme-linked immunospot assays and CTL assays. AGR2 was highly expressed in several CRC cell lines, including DK01, DLD1, KM12C, HCT-8 and HT-29. DCs pulsed with AGR2-P2 (aa 11-19; LLVALSYTL) or AGR2-P4 (aa 127-135; RIMFVDPSL) generated potent CTLs that could lyse T2 cells pulsed with AGR2-P2 or AGR2-P4 and HLA-A0201 AGR2-positive CRC cell lines in a strong dose-dependent and HLA*A0201-restricted manner. In conclusion, these novel epitopes derived from AGR2 protein may be attractive candidates for DC-based immunotherapy for CRC.

ISSN 

1672-7681

Link 

http://dx.doi.org/10.1038/cmi.2011.52

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2019-05-02


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