E-Poster Presentation 33rd Lorne Cancer Conference 2021

Novel High Affinity EGFRvIII CAR T Cells Effectively Eliminate Glioblastoma   (#128)

Rebecca C Abbott 1 , Daniel J Verdon 1 , Fiona M Gracey 2 , Hannah E Hughes-Parry 1 , Melinda Iliopoulos 1 , Kathy A Watson 1 , Matthias Mulazzani 1 , Kylie Luong 1 , Colleen Darcy 3 , Lucy C Sullivan 4 , Ben R Kiefel 2 , Ryan S Cross 1 , Misty R Jenkins 1 5 6
  1. Department of Immunology, The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia
  2. Myrio Therapeutics, Scoresby, Victoria, Australia
  3. Anatomical Pathology, Royal Children's Hospital, Parkville, Victoria, Australia
  4. Department of Microbiology and Immunology, Peter Doherty Institute, Parkville, Victoria, Australia
  5. Medical Biology, The University of Melbourne, Parkville, Victoria, Australia
  6. Institute for Molecular Science, La Trobe University, Bundoora, Victoria, Australia

Glioblastoma is an aggressive and lethal brain malignancy, accounting for approximately 60% of adult brain cancer diagnosis, and a 5 year survival rate of 5%. Treatment options for Glioblastoma have remained relatively unchanged for decades, and new treatments are urgently required. Chimeric antigen receptor (CAR) T cell therapy is a form of immunotherapy which redirects a patient’s own T cells to recognise and kill the malignant cells. We have characterised a novel CAR construct – C2, with a receptor specific for EGFRvIII – a tumour specific mutation in Glioblastoma. The C2 CAR was found to effectively kill Glioblastoma cells in vitro, and mediate complete tumour clearance in vivo as confirmed by histological analysis. The C2 CAR T cells were found to secrete lower levels of cytokines, including TNF-a, and RANTES, with a significant reduction in CCL3. However, CD8 C2 CAR T cells secreted higher quantities of IFN-g. This preclinical work will form the basis of future studies to evaluate the potential application of this C2 CAR to EGFRvIII+ Glioblastoma patients in the clinic.