Identification of immunoglobulin superfamily 11 (IGSF11) as a novel target for cancer immunotherapy of gastrointestinal and hepatocellular carcinomas

Abstract

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.

Identification of secernin 1 as a novel immunotherapy target for gastric cancer using the expression profiles of cDNA microarray

“…We have also shown that immunoglobulin superfamily 11 is a novel TAA that is expressed in gastric, colorectal and liver cancers, and reported antigenic epitope peptides for immunotherapy. (34) In this study, we have shown that SCRN1 is frequently expressed in gastric cancer and colon cancer tissues. Northern blot analysis also showed that expression of this gene is abundant in testis and ovary but barely detectable in other normal adult tissues examined.…”

Src Induces Podoplanin Expression to Promote Cell Migration

“…Kdr, which is also called Vefgr2, is a receptor for Vegfa (34), and can be targeted to prevent VEGF signaling and suppress angiogenesis required for malignant tumor growth (21). Antisera directed against IGSF11 can also be used to prevent tumor cell invasion and metastasis (22).…”

“…For example, inhibitors have been generated to target kinase insert domain receptor (Kdr) to prevent VEGF signaling and suppress angiogenesis required for malignant tumor growth (21). Immunological reagents have also been targeted to immunoglobulin superfamily 11 (IGSF11) (22) and Pdpn (23) to prevent tumor cell invasion and metastasis. …”

Gene Expression Profiling and Real-Time PCR Analyses Identify Novel Potential Cancer-Testis Antigens in Multiple Myeloma

“…We confirmed herein its expression in testis and brain but showed that IGSF11 is also expressed in adrenal gland. This gene is up-regulated in gastrointestinal and hepatocellular carcinomas, encodes a receptor essential for gastric cancer cell growth (34,35), and has been described as a novel immunogenic target since a natural HLA-A2-restricted T cell epitope was identified and a subsequent anchor-modified peptide was synthesized (35). TMEFF1 and TMEFF2, for transmembrane protein with EGF-like and two follistatin-like domains 1 and 2, respectively, encode putative growth factors predominantly expressed in the brain (36,37).…”