Abstract 3733: Defining and targeting a Glioblastoma cancer stem cell population with EGF Receptor Variant III.

Proceedings: AACR 104th Annual Meeting 2013; Apr 6-10, 2013; Washington, DC The relationship between mutated proteins and the relatively rare cancer stem cell population is unclear since driver mutations are present throughout a tumor. Glioblastoma (GBM) tumors frequently express EGFRvIII, an EGFR variant that arises via gene rearrangement and amplification. The expression of EGFRvIII is restricted despite the prevalence of the alteration. Here we show that EGFRvIII is expressed in a population of human GBM cancer stem cells. EGFRvIII positive cancer stem cells demonstrate greater self-renewal and tumor initiation than the more abundant EGFRvIII negative cells. EGFRvIII positive cells are associated with stem/progenitor markers while markers of differentiation are found in EGFRvIII negative cells. EGFRvIII is highly co-expressed with CD133, and the EGFRvIII positive/CD133 positive sub-population defines the highest self-renewal and tumor initiating population. Surprisingly, wildtype EGFR was infrequently co-expressed with EGFRvIII but present in the majority of cells, both in primary GBM and cultured GBM neurospheres. Elimination of the EGFRvIII positive or the EGFRvIII/CD133 dual positive population with an engineered anti-EGFRvIII/CD133 bi-specific antibody reduced tumorigenicity of implanted tumor cells. This work demonstrates that a mutated oncogene can have CSC specific expression and be used to specifically target this population. Citation Format: David R. Emlet, Catherine Del Vecchio, Puja Gupta, Siddhartha Mitra, Shuang-Yin Han, Marina Holgado-Madruga, Gordon Li, Kristen Jensen, Hannes Vogel, Stephen Skirboll, Albert J. Wong. Defining and targeting a Glioblastoma cancer stem cell population with EGF Receptor Variant III. [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 3733. doi:10.1158/1538-7445.AM2013-3733