Can you sum up the aim of this project in 10 words?
Teaching white blood cells to attack and destroy solid tumours
What have you previously discovered in this area?
We have found that T cells can be genetically engineered to express a new receptor (the Chimeric Antigen Receptor, or CAR), which then enables them to bind and kill cancer cells that express the target molecule. However, we have also discovered that once infused into patients these CAR T-cells struggle to persist and control solid tumours. This is in contrast to the impressive results seen for CAR T-cells in the treatment of CD19+ haematological cancers. We are now working to improve CAR T-cell technology with the hope that patients with advanced solid tumours will then be able to benefit from the treatment.
What will this project entail?
In this project we take blood from cancer patients, purify the white blood cells, and use genetic engineering to manufacture a CAR T-cell product. We have found a way to keep these cells relatively ‘young’ while they are being grown and expanded in the lab, so that when they get infused back in to the patient they will have the best chance of persisting, trafficking to the tumour and then exerting their anti-tumour effect. We will be testing these new and improved CAR T-cells in patients with melanoma, sarcoma, triple-negative breast cancer and small cell lung cancer at the Royal Adelaide Hospital.
What aspect of this research excites you the most?
Unleashing the power of the immune system against cancer has been a goal for researchers in the immunotherapy field for decades. In just the last 10 years we have seen two breakthrough treatments: CAR T-cells for CD19+ leukemias and immune checkpoint inhibitors (anti-CTLA-4 and anti-PD1 monoclonal antibodies) for melanoma. The race is now on to realise the promise of these immunotherapies for other cancers, so it’s incredibly exciting to be working in this space.
What is the difference between CAR T-cells in solid versus haematological cancers?
CAR T-cells that treat haematological cancers meet their target cells the instant they are infused into the blood. They don’t have to fight their way into tissue to reach a tumour and they don’t have to overcome the wide range of immune-suppressive mechanisms that the tumour microenvironment is capable of. In addition, the CD19 target is also uniformly expressed on every (or almost every) cancer cell and on very few healthy cells, whereas we are yet to find a universal target for solid cancers.
How long before this work might impact patient care?
We are already seeing an impact for patients in the US, with CD19-specific CAR T-cell therapy FDA-approved and soon to be available for patients here in Australia as well. I don’t think it’s unreasonable to think that in the next 5-10 years we will see further approvals for other CAR T-cell products.
What’s your Holy Grail – the one thing you’d like to achieve in your research career?
I’d like to find a CAR T-cell treatment or other immunotherapeutic approach that would benefit patients with brain cancers such as glioblastoma in adults and diffuse midline glioma in children. These are devastating diseases with terrible 5-year survival rates and almost no treatment options. Immune checkpoint inhibitors don’t appear to benefit these patients but it’s possible CAR T-cells might.
What is your biggest research hurdle?
Too many ideas and not enough hours (and PhD students)! But on a scientific level the tumour microenvironment – it has developed in such a way that it actively suppresses and rejects attempts by the immune system to destroy it. This is the main hurdle that has to be overcome for CAR T-cells in solid tumours and may well require a combination therapy approach.
Who has inspired you in work or life?
I am inspired by the patients who agree to participate in phase 1 trials, despite knowing how unlikely it is to benefit themselves. When you ask them, they just say they hope that they’ll be helping someone else. That’s incredibly altruistic.
‘There’s an app for that.’ What’s new on your phone?
Well, before my 2-year-old dropped my phone in the toilet it was the Kinderling Kids Radio app!