WEHI PhD Completion Seminar hosted by Professor Misty Jenkins

Zoe Day

PhD Student – Jenkins Laboratory, Brain Cancer Centre – Personalised Oncology division, WEHI

Graduate Researcher – Biochemistry – Hulett Laboratory, La Trobe Institute for Molecular Science (LIMS) – La Trobe University

Exploring Multi-Modal Therapeutic Strategies for Solid Tumours: Integrating Small Molecule-Induced Cell Death and CAR T Cell Based Immunotherapy Approaches

 

L7W Seminar Room

Join via SLIDO enter code #WEHIphdcompletion

Including Q&A session

Followed by refreshments in Boardroom

Solid tumours, including high-grade gliomas such as glioblastoma and diffuse midline gliomas, remain major contributors to cancer mortality, with limited therapeutic progress over recent decades. For patients, this means survival rates remain abysmal, with at best a 5% 5-year survival rate. Hence, my PhD conducted with dual affiliations at the Walter and Eliza Hall Institute and La Trobe Institute for Molecular Science, explores novel strategies to overcome key barriers in solid tumour treatment—namely, resistance to cell death, the immunosuppressive extracellular matrix (ECM), and antigenic heterogeneity.

In collaboration with Wintermute Biomedical two water-soluble fatty acid formulations were developed: GS-1, inducing apoptosis via undecylenic acid, and GS-9, a ferroptosis-inducing arachidonic acid compound. These agents demonstrate mechanistically distinct, targetable forms of tumour cell death with translational potential.

Further, taking a closer look at high-grade gliomas we performed one of the first comprehensive analyses of the ECM of these aggressive brain tumours. Using histologic, proteomic and transcriptomic profiling of primary adult and paediatric gliomas we identified a number of tumour-enriched ECM components and targets such as GPC2 and CSPG4. CAR T cells directed against GPC2 showed effective cytotoxicity, establishing the ECM as a viable immunotherapeutic niche. Together, this research contributed not only to our understanding of the ECM and underlying biology of these tumours but also contributed to the paradigm shift of the ECM not just being seen as a structural component of the tumour microenvironment but also an immunologically targetable feature of these tumours.

Lastly, the study characterizes a novel High-Grade glioma antigen and validates CAR T cells against this target using a high throughput screening pipeline that I helped to develop through the later part of my PhD. Together, these findings define new therapeutic axes for treating high-grade gliomas and other solid tumours, combining cell death induction, ECM-targeted immunotherapy, and novel antigen discovery and CAR T cell development to inform the next generation of solid tumour treatments to improve patient outcomes.

All welcome!