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EGFRvIII-IL13Ra2-DTriTE is a DNA-encoded tri-specific T cell engager (DTriTE) designed for the treatment of glioblastoma multiforme (GBM). Developed by researchers at the University of Pennsylvania and The Wistar Institute, this therapeutic utilizes a DNA plasmid platform to achieve sustained in vivo expression of a tri-specific protein following a single intramuscular injection. The expressed protein consists of single-chain variable fragments (scFvs) that simultaneously target two tumor-associated antigens, epidermal growth factor receptor variant III (EGFRvIII) and interleukin-13 receptor alpha 2 (IL13Ra2), while also binding to the CD3 epsilon chain on T cells. This multi-antigen targeting strategy is intended to address the significant antigenic heterogeneity of GBM and prevent tumor escape. Preclinical data presented at AACR 2023 demonstrated that a single administration of the DTriTE construct led to complete tumor clearance and significantly improved survival in orthotopic GBM models compared to bispecific T cell engagers.
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