With her team, she discovered that, when target cells do not die quickly, it can cause inflammation, which hampers the body’s immune response.
Even though cancer survival rates have increased and cancer mortality rates continue to drop, cancer accounts for around three of every 10 deaths in Australia. Aboriginal and Torres Strait Islander people and people in lower socioeconomic groups have even lower cancer survival rates than other Australians.
Australian Institute of Health and Welfare. “Cancer in Australia 2019” Australian Government. 21 March 2019. Accessed 25 August 2020. https://www.aihw.gov.au/reports/cancer/cancer-in-australia-2019/contents/summary
Associate Professor Misty Jenkins is an NHMRC fellow and Laboratory Head in the Immunology Division at The Walter and Eliza Hall Institute of Medical Research, where she researches cancer immunotherapy — a treatment which utilises the body’s immune system to treat cancerous cells.
Associate Professor Jenkins has a long-standing interest in CD8+ T cell — or ‘killer’ T cell — cytotoxicity, with her current research program focusing on killer T cell immunotherapy for brain cancer.
“Killer T cells are a specialised group of immune cells which destroy cancerous and infected cells.
When killer T cells find a target — like a cancer or infected cell — they attach and secrete toxic molecules. They then detach from the dying target, so that they may go on to kill other cells. If they don’t detach properly, they remain bound to the target cell, which can result in an improper immune response.”
“Outcomes for patients with high-grade brain and spinal tumours are currently poor, but if we can design efficient T cell immunotherapies that kill tumours without causing inflammation in the brain, we might be able to help people.”
This NHMRC Project Grant was awarded to shed light on how the killer T cell detaches, which is essential for an effective immune response.
“This grant enabled further research to understand how white blood cells and natural killer cells kill their cancerous targets one after the other, sometimes referred to as ‘serial killing’. Decades ago, researchers coined the term ‘kiss of death’ for this fatal interaction,” Associate Professor Jenkins said.
The study also showed how engineered chimeric antigen receptor T cells (CAR T cells) formed an immune synapse with their targets — the vital connection that controls how the cells function. This research unveiled how these synthetic receptors on CAR T cells, which are currently being used to treat a variety of cancers, can override the killing capacity of T cells and in fact may result in faster signalling of the T cell. This information can be used to design even more effective killing receptors to target a variety of cancer types.
Associate Professor Jenkins and her team have been able to make predictions about the efficiency of killer T cells, which is important for designing new immunotherapies. Together, they are excited to take these findings from the laboratory into the clinic. “In our current program, we are generating novel immunotherapies to treat brain cancer in both adult and paediatric patients.”