AGY’s oncology antibody program initially focused on the identification of proteins selectively expressed by brain tumors and on the development of therapeutics for the treatment of glioblastoma multiforme. Further studies of these targets in a number of additional solid tumors suggest that they may have utility beyond glioblastoma multiforme treatment.

AGY studied brain tumors through the transcriptional profile analysis of primary human samples from surgical biopsies using its proprietary imAGYne™ array-based discovery platform and powerful bioinformatics analysis. We identified numerous genes whose expression is up-regulated specifically in a large proportion of tumor samples at various stages of glioma and in the majority of cells within a given sample. Using in-situ hybridization and immunohistochemistry techniques, we have confirmed and expanded upon our studies of glioblastoma-specific up-regulated genes in over 100 human brain tumor samples. The work performed by AGY has produced data on target expression level and distribution within tumors and in normal brains. We have identified highly specific targets for therapeutic intervention and possibly diagnostic purposes. The extracellular domains of all three targets were expressed and purified and used as antigens for immunization of mice and subsequent generation of monoclonal antibodies. The lead antibodies are potent and selective and bind to the surface of glioma cells. Moreover, when conjugated with a toxin they are able to kill glioma cells.

AGY-401 is a receptor tyrosine phosphatase and has been implicated in controlling migration of glioma cells. AGY-401 interacts with extracellular matrix proteins and controls the invasive behavior for tumor cells. By specific knock-down of AGY-401 gene expression using siRNA in glioblastoma cell lines, we were able to show that the migration of glioblastoma cells is inhibited. AGY-401 is also expressed in colon, breast, skin and lung cancer samples.

AGY-402 is a member of a novel class of tyrosine kinases that bind to several collagens and stimulate the expression of matrix metalloproteinases. We showed that expression of AGY-402 in gliobastoma cells stimulates matrix degradation and basement membrane invasion. AGY-402 is also expressed in colon, breast, skin and lung cancer samples.

AGY-403 is an orphan G protein coupled receptor (GPCR) with a large N-terminal domain belonging to the secretin-like receptor family. We showed that this protein is overexpressed in a majority of high-grade gliomas. Using blocking antibodies, biochemical assays and immunofluorescence-based localization, we demonstrated that this protein is involved in adhesion. AGY-403 is also expressed in colon, lung, skin and prostate cancer samples.

AGY has established a broad intellectual property position for the most valuable targets and lead compounds. In addition, the company established an intellectual property portfolio protecting its key technologies, including molecular cloning, bioinformatics for pathways, as well as the use of RNA interference (RNAi) in neurons and glial cells.
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