When someone asks me to explain my work, I ask them if they know of anyone who has been affected by a disease caused by the immune system not functioning as it should. And pretty much all of us do. I lost my grandfather to cancer, and I see a lot of friends and family suffering through multiple diseases – even everyday allergies are related to your immune system.
To understand the function of our immune system is to understand the fundamentals of our ability to combat disease. Yet one of the most striking things I see is how broad and damaging different treatments are for some of these diseases. With cancer, for example, we know there are treatments like chemotherapy and radiotherapy that could work, but we often have that sinking feeling that they may not.
This is one of the most impactful areas where we can make advances through immunology. In our bloodstream there are millions of blood cells. Some of these cells are designed to be very specialised, and are called T cells. These T cells are part of the immune system that play a critical role in seeing foreign antigens and fighting disease – this is the area of research that Peter Doherty was awarded the Nobel Prize for in 1995. My research assesses all the different types of T cells, which we suspect have very specific functions. And the more we look, the more we see that some types are understudied.
We strongly believe that T cells have the potential to treat a wide range of disease. But there is so much we don’t know. Basically, it’s like we’ve been flying a plane without knowing how everything works – what each set of T cells actually does. The next big thing in our understanding of many diseases will come through our efforts in building an encyclopaedia of T cells so that we have a catalogue of what they are and what they all do.
The T? That stands for thymus. It was actually a French-Australian researcher, Professor Jacques Miller, who discovered back in the early 1960s that T cells are manufactured and given their instructions by the thymus – he is one of the last people in the world who can say that they actually discovered the role of a functioning organ.
The thymus sits in the upper front part of our chest, behind the sternum, in front of our heart. I think Professor Miller looked at this tissue and realised it couldn’t just be a cup of fat tissue above the heart – there had to be something in there. He discovered that T cells are actually educated in this organ.
So we now know that T cells are involved in fighting every invasive pathogen in the human body, but there’s a problem with T cells that we’re trying to understand. It comes back to Peter Doherty’s discovery, that our T cells are bespoke to each individual. Which means that I can’t just transfer my T cells into you, or yours into me. If you have ever heard of transplant issues, for example, and why organs get rejected, it comes down to this basic issue that our T cells aren’t all compatible with one another.
In fact, we’ve made a fairly new discovery about T cell compatibility, focusing on a population of T cells – innate T cells, where these ones see universal patterns that exist in all of us. If we can fully understand this pattern recognition, we have a unique opportunity. It will be like a key to unlock T cell therapy.
We could access T cells that are universally transferable between healthy donors and patients. This is a game changer to bypass the current challenges of using a patient’s own T cells – because they might already be compromised because of the disease. We just have to find out more about innate-T cells to unlock them.
This is what really excites me. I’m studying the basic biology of these innate T cells. How many are there? Do we all have different numbers of them to begin with? How do they even develop in the body? What keeps them going at a steady state in our body? Can they be different in terms of function? Is there some way we can control their function one way or another? And how do we expand that so that we can use them in immunotherapy?
The goal in my work is to understand mechanisms that control innate T cells so that we can then create a better T cell therapy. Every piece of evidence would culminate towards the ultimate ambition of the field, which is off-the-shelf, tailored T cell therapy. To illustrate this, let’s say a patient needs 50 million of these cells to combat a specific cancer, and we have generated banks of healthy innate T cells which we know function against the cancer – we can now put them into the patient.
There’s also a patch of blue sky that we might speculate about to describe the vast potential of these universal T cells. Let’s imagine that because of antimicrobial resistance we don’t have effective antibiotics in the future to kill bacteria. There are exciting possibilities to generate off-the-shelf innate T cell products that can be directed against antibiotic resistant microbes, that could represent the next generation of anti-bacterial treatment.
Once we fully understand T cells, the sky is the limit.
As told to Graem Sims for Cosmos Weekly