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Updated: Nov 6, 2025
Generation of CAR T Cells for Adoptive Therapy in the Context of Glioblastoma Standard of Care
Published on: February 16, 2015
Novel high-affinity EGFRvIII-specific chimeric antigen receptor T cells effectively eliminate human glioblastoma
Rebecca C Abbott1,2, Daniel J Verdon1, Fiona M Gracey3
1Immunology Division The Walter and Eliza Hall Institute of Medical Research Parkville VIC Australia.
Objectives:
The increasing success of Chimeric Antigen Receptor (CAR) T cell therapy in haematological malignancies is reinvigorating its application in many other cancer types and with renewed focus on its application to solid tumors. We present a novel CAR against glioblastoma, an aggressive, malignant glioma, with a dismal survival rate for which treatment options have remained unchanged for over a decade.
Methods:
We use the human Retained Display (ReD) antibody platform (Myrio Therapeutics) to identify a novel single-chain variable fragment (scFv) that recognises epidermal growth factor receptor mutant variant III (EGFRvIII), a common and tumor-specific mutation found in glioblastoma. We use both in vitro functional assays and an in vivo orthotopic xenograft model of glioblastoma to examine the function of our novel CAR, called GCT02, targeted using murine CAR T cells.
Results:
Our EGFRvIII-specific scFv was found to be of much higher affinity than reported comparators reverse-engineered from monoclonal antibodies. Despite the higher affinity, GCT02 CAR T cells kill equivalently but secrete lower amounts of cytokine. In addition, GCT02-CAR T cells also mediate rapid and complete tumor elimination in vivo.
Conclusion:
We present a novel EGFRvIII-specific CAR, with effective antitumor functions both in in vitro and in a xenograft model of human glioblastoma.
