Identification of immunoglobulin superfamily 11 (IGSF11) as a novel target for cancer immunotherapy of gastrointestinal and hepatocellular carcinomas.
We previously performed gene expression profile analyses of 20 intestinal-type gastric cancers, and identified a set of genes whose expression levels were elevated in cancer tissues compared to their corresponding non-cancerous tissues. In the present study we focused on the immunoglobulin superfamily 11 gene (IGSF11). Its expression was also elevated in colorectal cancers and hepatocellular carcinomas as well as intestinal-type gastric cancers. Northern blot analysis showed that it was expressed abundantly in testis and ovary. These data suggest that IGSF11 is a good candidate of cancer-testis antigen. Furthermore, suppression of IGSF11 by siRNA retarded the growth of gastric cancer cells. To investigate the possibility of clinical application of peptide vaccine to IGSF11, we synthesized candidate epitope peptides for IGSF11 and tested whether the peptides elicit IGSF11-specific CTL. As a result, we successfully established oligo-clonal CTL by stimulation with IGSF11-9-207 (ALSSGLYQC). In addition, we also established additional CTL using IGSF11-9V (ALSSGLYQV), anchor-modified peptides of IGSF11-9-207. These peptides showed IGSF11-specific cytotoxic activity in an HLA-A*0201-restricted fashion, suggesting that these peptides may be applicable for cancer immunotherapy. These findings have provided a novel insight into carcinogenesis of the stomach, colon and liver, and will be helpful for the development of novel therapeutic strategies to a wide range of human cancers.
Watanabe
Takeshi
T
Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, The University of Tokyo, 4-6-1, Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.
Suda
Takako
T
Tsunoda
Takuya
T
Uchida
Naotaka
N
Ura
Katsuaki
K
Kato
Tatsushi
T
Hasegawa
Suguru
S
Satoh
Seiji
S
Ohgi
Shigetsugu
S
Tahara
Hideaki
H
Furukawa
Yoichi
Y
Nakamura
Yusuke
Y
D016475:3T3 Cells; D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000276:immunology*; D015815:Cell Adhesion Molecules / Q000235:genetics*; D002455:Cell Division / Q000235:genetics; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms; D005770:Gastrointestinal Neoplasms / Q000276:immunology*; D006023:Glycoproteins / Q000235:genetics*; D006801:Humans; D007136:Immunoglobulins / Q000235:genetics*; D007167:Immunotherapy / Q000379:methods*; D008113:Liver Neoplasms / Q000276:immunology*; D008297:Male; D051379:Mice; D020033:Protein Isoforms / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013274:Stomach Neoplasms; D013736:Testicular Neoplasms
D015815:Cell Adhesion Molecules; D006023:Glycoproteins; C482101:IGSF11 protein, human; D007136:Immunoglobulins; D020033:Protein Isoforms