Novel high-affinity EGFRvIII-specific chimeric antigen receptor T cells effectively eliminate human glioblastoma
Details
Publication Year 2021, Volume 10, Issue #5, Page e1283
Journal Title
Clinical & Translational Immunology
Abstract
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.
Publisher
Wiley
Keywords
CAR T cells; Chimeric Antigen Receptor (CAR); EGFRvIII; T cells; brain cancer; glioblastoma; immunotherapy
WEHI Research Division(s)
Immunology
PubMed ID
33976881
Publisher's Version
https://doi.org/10.1002/cti2.1283
Open Access at Publisher's Site
https://doi.org/10.1002/cti2.1283
Rights Notice
Refer to copyright notice on published article.


Creation Date: 2021-05-17 11:04:06
Last Modified: 2021-05-17 11:08:31
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