RT Journal Article
SR Electronic
T1 Ring Finger Protein 43 as a New Target for Cancer Immunotherapy
JF Clinical Cancer Research
JO Clin Cancer Res
FD American Association for Cancer Research
SP 8577
OP 8586
DO 10.1158/1078-0432.CCR-04-0104
VO 10
IS 24
A1 Uchida, Naotaka
A1 Tsunoda, Takuya
A1 Wada, Satoshi
A1 Furukawa, Yoichi
A1 Nakamura, Yusuke
A1 Tahara, Hideaki
YR 2004
UL http://clincancerres.aacrjournals.org/content/10/24/8577.abstract
AB We have performed genome-wide exploration by using cDNA microarray profiling, and successfully identified a new tumor-associated antigen (TAA) that can induce potent cytotoxic T lymphocytes (CTLs) specific to tumor cells. In our preceding study, we identified multiple new genes by using gene expression profiling with a genome-wide cDNA microarray containing 23,040 genes. Among them, we selected RNF43 (ring finger protein 43) as a promising candidate for a TAA expressed by colon cancer cells. In this study, we examined whether the RNF43 protein contains antigenic epitope peptides restricted to HLA-A*0201 or HLA-A*2402. The CTL clones were successfully induced with stimulation by using the peptides binding to HLA-A*0201 (ALWPWLLMA and ALWPWLLMAT) and HLA-A*2402 (NSQPVWLCL), and these CTL clones showed the cytotoxic activity specific to not only the peptide-pulsed targets but also the tumor cells expressing RNF43 and respective HLAs. Lytic activities mediated by two HLA-A2-restricted epitopes were marginal, whereas tumor lysis mediated by the HLA-A24 epitope was clearly better. These findings might be caused by the poor natural presentation of RNF43-11(IX) and RNF43-11(X) by tumors or poor T-cell receptor avidity for these specific epitopes. These results strongly suggest that RNF43 is a new TAA of colon cancer. Furthermore, these results also suggest that our strategy might be a promising one to efficiently discover clinically useful TAAs.