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Abstract 2047: Discovery and molecular characterization of AGS-15/SLITRK6 as a novel target for antibody-mediated therapeutic development in bladder cancer.

Proceedings: AACR 104th Annual Meeting 2013; Apr 6-10, 2013; Washington, DC

Discovery efforts utilizing suppression subtractive hybridization identified AGS-15/SLITRK6 as a differentially expressed gene in bladder cancer. SLITRK6 encodes a cell surface type I transmembrane protein, a member of the SLITRK family of factors with neuronal function activities. Comprehensive SLITRK6 RNA expression analysis in patient specimens revealed limited restricted normal tissue expression and high frequent expression in bladder cancers, as well as expression in subsets of breast, lung and several other cancer types. Tissue immunohistochemical analysis validated SLITRK6 protein limited expression in normal tissues and high expression levels in cancers. SLITRK6 expression profiling in cancer cell lines and Agensys proprietary patient-derived xenografts (PDXs) identified model systems in relevant cancer indications for further target characterization and antibody therapeutics development. Genomic analyses, including whole exome next generation sequencing, chromosomal aberrations and gene copy number assessments, were performed to evaluate SLITRK6 gene status in model cell lines and PDXs. Thus, we discovered and characterized AGS-15/SLITRK6 as a novel target with high levels and selective expression in tumors, particularly in bladder cancer. This cell surface antigen's attractive expression profile is a major determinant of AGS-15/SLITRK6 as a suitable and preferential candidate for antibody drug conjugate therapeutic targeting in bladder cancer treatment and, potentially, in several other cancer indications.

Citation Format: Yuriy Shostak, Suzanne Said, Deanna L. Russell, Michael D. Mattie, Mi Sook Chang, Ashley Christensen, Karen Morrison, Kendall Morrison, David Stover, Pia Challita-Eid. Discovery and molecular characterization of AGS-15/SLITRK6 as a novel target for antibody-mediated therapeutic development in bladder cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2047. doi:10.1158/1538-7445.AM2013-2047