Journal article
Human EGFRvIII chimeric antigen receptor T cells demonstrate favorable safety profile and curative responses in orthotopic glioblastoma
RC Abbott, M Iliopoulos, KA Watson, V Arcucci, M Go, HE Hughes-Parry, P Smith, MJ Call, RS Cross, MR Jenkins
Clinical and Translational Immunology | WILEY | Published : 2023
DOI: 10.1002/cti2.1440
Abstract
Objectives: Glioblastoma is a highly aggressive and fatal brain malignancy, and effective targeted therapies are required. The combination of standard treatments including surgery, chemotherapy and radiotherapy is not curative. Chimeric antigen receptor (CAR) T cells are known to cross the blood–brain barrier, mediating antitumor responses. A tumor-expressed deletion mutant of the epidermal growth factor receptor (EGFRvIII) is a robust CAR T cell target in glioblastoma. Here, we show our de novo generated, high-affinity EGFRvIII-specific CAR; GCT02, demonstrating curative efficacy in human orthotopic glioblastoma models. Methods: The GCT02 binding epitope was predicted using Deep Mutational ..
View full abstractGrants
Awarded by Royal Melbourne Hospital
Funding Acknowledgements
We thank the following for financial support: National Health and Medical Research Council (NHMRC) (Synergy Grant APP2010849), Robert Connor Dawes Foundation, Carrie's Beanies for Brain Cancer and Isabella and Marcus Foundation. This was made possible in part and financially supported through the author's membership in the Brain Cancer Centre. MRJ is funded by NHMRC Investigator Grant (APP1172858). RSC was funded by Cure Brain Cancer Foundation Fellowship. We thank Rodney Luwor (Royal Melbourne Hospital, the University of Melbourne) for providing cell lines. We thank Dr Vaughan Feisst and Dr Daniel Verdon for the keratinocyte growth media and supplement recipes. We thank Dr Jim Whittle, Dr Ruth Mitchell, Professor Kate Drummond and Professor Mark Rosenthal for their helpful discussions. We thank Professor Andrew Scott and Hui Gan (Olivia Newton-John Cancer Research Institute, Melbourne) for providing the anti-EGFRvIII monoclonal antibody used in immunohistochemistry (LMH-151).<SUP>42</SUP> We acknowledge Pete Smith, Dr Matt Beasley and Dr Ben Kiefel at Myrio Therapeutics Pty Ltd for developing the GCT02 binder.<SUP>18</SUP> The DMS library was created with the help of the WEHI Multiplexed Assay Technology Hub, which was founded with WEHI New Medicines and Advanced Technology Theme funding.