WEHI Wednesday Seminar hosted by Professor Misty Jenkins

Krishneel Prasad

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

Developing Effective and Regulatable CAR T Cell Therapies for Brain Cancer and other Solid Tumours

Davis Auditorium

Join via SLIDO enter code #WEHIWednesday

Including Q&A session

https://app.sli.do/event/tTFyw9GbY9rKB8uua4pKrk

Glioblastoma is an aggressive brain cancer where 5-year survival rates have remained at 5% for decades. Chimeric Antigen Receptor (CAR) T cell therapies are emerging as promising treatment options, with recent clinical trials reporting cases of tumour regression and improved survival. However, treatment related toxicities and cytokine release syndrome still require careful management.  

The Jenkins Laboratory has applied cell surface proteomics to primary brain tumour tissue to uncover novel immunotherapeutic targets, leading to the identification of the heat shock protein HSP90B1. Typically localised to the Endoplasmic Reticulum, HSP90B1 undergoes cell surface mis-localisation in stressed and proliferative cells, making it an attractive cancer target. Our HSP90B1 CAR T cells displayed pan-cancer activity in vitro and demonstrated potent in vivo tumour protection in glioblastoma and colon cancer models. Ongoing validation of tumour specificity positions stress response proteins as an under-exploited antigen class for cancer immunotherapy. 

Versatile Protease Regulatable CAR (VIPER) T cells employ a split CAR design that can be inhibited by grazoprevir, an FDA-approved antiviral agent. Applying this technology to brain cancer, we screened a library of 16 CARs to determine a ruleset for CARs converted into VIPERs. In vitro assessment across multiple solid tumour models identified B7-H3-, HSP90B1-, and HER2-targeting VIPER T cells as effective therapies with functional, tuneable off-switches.  

Next-generation T cell therapies, whether through multi-antigen targeting or armouring, are increasingly necessary to tackle solid tumours. Together, these studies identify an under-explored antigen class for cancer targeting and demonstrate VIPERs as a versatile platform for engineering drug-regulatable cell therapies against solid tumours. 

All welcome!