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

作　　者：Hyun Ju Lee Cheol Yi Hong Chun-Ji Jin Mi-Hyun Kim Youn-Kyung Lee Thanh-Nhan Nguyen-Pham Hyunah Lee Byoung Chul Park Ik-Joo Chung Hyeoung-Joon Kim Je-Jung Lee 

机构地区：[1]Research Center for Cancer Immunotherapy, Chonnam National University Hwasun Hospital, Hwasun, Jeollanamdo, Korea [2]Department of Hematology-Oncology, Chonnam National University, Gwangju, Korea [3]VaxcelI-Bio Therapeutics, Hwasun, Jeollanamdo, Korea [4]Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea [5]Korea Research Institute of Bioscience and Biotechnology （KRIBB）, Daejeon, Korea [6]The Brain Korea 21 Project, Center for Biomedical Human Resources at Chonnam National University, Gwangiu, Korea

出　　处：《Cellular & Molecular Immunology》2012年第2期175-183,共9页中国免疫学杂志（英文版）

摘　　要：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）-A 0201-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-A 0201 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, KM 12C, 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-A 0201-restricted manner. In conclusion, these novel epitopes derived from AGR2 protein may be attractive candidates for DC-based immunotherapy for CRC.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）-A 0201-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-A 0201 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, KM 12C, 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-A 0201-restricted manner. In conclusion, these novel epitopes derived from AGR2 protein may be attractive candidates for DC-based immunotherapy for CRC.

关 键 词：AGR2 colorectal cancer dendritic cell tumor-associated antigen 

分 类 号：Q347[生物学—遗传学] Q987.2