Chimeric Antigen Receptor Immunotherapy approaches for brain cancer

Abstract

Glioblastoma is an aggressive and highly malignant brain tumour with a dismal 5-year survival rate of just 5%. New and targeted treatments for glioblastoma are urgently required. Chimeric Antigen Receptor (CAR) T cell therapy has shown early promise for brain tumours, and unlike other drugs, living T cells can effectively cross the blood brain barrier and infiltrate brain tumours.  However, a major constraint to the expansive use of CAR T cells more broadly is identifying suitable targets. Despite sequencing tumours for decades, there is a poor correlation between RNA and protein, and in particular the cell surface proteome of brain tumours remains poorly characterised. In order to address this and progress new immunotherapy treatments, we have been mapping the glioblastoma tumour surface proteome and uncovered novel biomarkers of the disease.

In this talk, I will discuss the development of our pipeline to discover new CAR T cell targets, and present data of our novel binders to well established glioblastoma targets. I will present our early approaches in using logic gating for multitargeting of glioblastoma using CAR T cells and discuss the role of that microglia plays in mediating immunosuppression. Our strategy for developing a robust immunotherapy platform within the newly established brain cancer centre will be discussed.

Biography

Misty Jenkins is a NHMRC fellow and laboratory head in the Immunology Division at Walter and Eliza Hall Institute for Medical Research, where she researches cellular immunology and cancer immunotherapy.  Misty leads the immunotherapy program within the Brain Cancer Centre and is dedicated to developing new treatments for brain cancer patients. Misty studied her PhD in Immunology at The University of Melbourne, followed by postdoctoral positions at The Universities of Cambridge and Oxford, and The Peter MacCallum Cancer Centre in Melbourne. Misty has a long-standing interest in CD8⁺ T cells and her research program researches the use of T cell immunotherapy for brain cancer. A/Prof Jenkins was awarded the L’Oreal for Women in Science Fellowship (2013), was Tall Poppy of the year (2015), was awarded the Westpac/Australian Financial Review Top100 Women of Influence award (2016) and was inducted onto the Victorian Honour Roll of Women in 2020. In addition to her research career, A/Prof Jenkins is experienced in governance and is a Board Director for Monash Health, Co-Chair of the Indigenous Health Medical Research Future Fund, and advises the Victorian Government on Health and Medical Research strategy.