WEHI Wednesday Seminar hosted by Professor Misty Jenkins
Leesa Lertsumitkul PhD Student – Jenkins Laboratory, Brain Cancer Centre – Personalised Oncology division, WEHI (this is a PhD Completion seminar)
Developing novel targeted CAR T cell therapies for high-grade gliomas
Davis Auditorium Join via SLIDO enter code #WEHIWednesday
Including Q&A session
High-grade gliomas, such as glioblastoma (GBM) and diffuse midline gliomas (DMG), are relatively rare brain cancers but are highly aggressive and remain incurable. Current treatment options of surgery, chemotherapy and radiotherapy have not changed in over 20 years and survival rates remain abysmal – a median survival rate of 1-2 years for GBM and < 1 year for DMG. Next-generation cellular therapies including chimeric antigen receptor (CAR) T cell therapies have been transformative in treating haematological malignancies. Now the field is looking to translate this success into solid tumours, particularly brain cancer. Optimal selection of target antigens remains one of the key challenges for CAR T cell therapies treating solid tumours due to their heterogenous antigen expression and the risk of causing on-target off-tumour toxicities.
To establish a clinically relevant novel target discovery platform, our group have employed cell surface proteomic analysis of high-grade glioma patient samples to map the most abundant cell surface proteins. We identified a key protein, Ephrin type-A receptor 3 (EphA3), as prevalently expressed within this patient cohort. My PhD has focused on developing a novel EphA3-targeted CAR T cell therapy and validating its efficacy in preclinical models of GBM and DMG. Using orthotopic xenograft mouse models, I have demonstrated that this novel CAR T cell therapy exhibits a robust anti-tumour effect, resulting in complete and sustained tumour clearances. I also discovered that these CAR T cells formed a functional memory T cell population that was protective upon a second tumour challenge. My findings provide compelling preclinical evidence supporting the efficacy of EphA3-targeted CAR T cells for the treatment of high-grade gliomas, demonstrating promising potential for clinical translation. My seminar will outline the current landscape of CAR T cell therapies in brain cancer research and how my work contributes to this evolving field.