PMID- 22231555 OWN - NLM STAT- MEDLINE DCOM- 20120709 LR - 20211021 IS - 2042-0226 (Electronic) IS - 1672-7681 (Print) IS - 1672-7681 (Linking) VI - 9 IP - 2 DP - 2012 Mar TI - Identification of novel HLA-A*0201-restricted epitopes from anterior gradient-2 as a tumor-associated antigen against colorectal cancer. PG - 175-83 LID - 10.1038/cmi.2011.52 [doi] AB - 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, 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-A*0201-restricted manner. In conclusion, these novel epitopes derived from AGR2 protein may be attractive candidates for DC-based immunotherapy for CRC. FAU - Lee, Hyun Ju AU - Lee HJ AD - Research Center for Cancer Immunotherapy, Chonnam National University Hwasun Hospital, Hwasun, Jeollanamdo, Korea. FAU - Hong, Cheol Yi AU - Hong CY FAU - Jin, Chun-Ji AU - Jin CJ FAU - Kim, Mi-Hyun AU - Kim MH FAU - Lee, Youn-Kyung AU - Lee YK FAU - Nguyen-Pham, Thanh-Nhan AU - Nguyen-Pham TN FAU - Lee, Hyunah AU - Lee H FAU - Park, Byoung Chul AU - Park BC FAU - Chung, Ik-Joo AU - Chung IJ FAU - Kim, Hyeoung-Joon AU - Kim HJ FAU - Lee, Je-Jung AU - Lee JJ LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20120109 PL - China TA - Cell Mol Immunol JT - Cellular & molecular immunology JID - 101242872 RN - 0 (AGR2 protein, human) RN - 0 (Antigens, Neoplasm) RN - 0 (Epitopes) RN - 0 (HLA-A*02:01 antigen) RN - 0 (HLA-A2 Antigen) RN - 0 (Mucoproteins) RN - 0 (Oncogene Proteins) RN - 0 (Peptide Fragments) RN - 0 (Proteins) SB - IM MH - Antigen Presentation MH - Antigens, Neoplasm/genetics/*immunology MH - Cell Line, Tumor MH - Coculture Techniques MH - Colorectal Neoplasms/genetics/*immunology/pathology/*therapy MH - Computational Biology MH - Cytotoxicity, Immunologic MH - Dendritic Cells/immunology/transplantation MH - Enzyme-Linked Immunospot Assay MH - Epitope Mapping MH - Epitopes/genetics/immunology MH - HLA-A2 Antigen/*immunology MH - Humans MH - *Immunotherapy MH - Lymphocyte Activation MH - Mucoproteins MH - Oncogene Proteins MH - Peptide Fragments/genetics/immunology MH - Protein Binding MH - Proteins/genetics/*immunology MH - T-Lymphocytes, Cytotoxic/immunology/*metabolism/pathology PMC - PMC4002806 EDAT- 2012/01/11 06:00 MHDA- 2012/07/10 06:00 PMCR- 2012/03/01 CRDT- 2012/01/11 06:00 PHST- 2012/01/11 06:00 [entrez] PHST- 2012/01/11 06:00 [pubmed] PHST- 2012/07/10 06:00 [medline] PHST- 2012/03/01 00:00 [pmc-release] AID - cmi201152 [pii] AID - 10.1038/cmi.2011.52 [doi] PST - ppublish SO - Cell Mol Immunol. 2012 Mar;9(2):175-83. doi: 10.1038/cmi.2011.52. Epub 2012 Jan 9.