Researchers at the Garvan Institute of Medical Research have been exploring ways to make interleukin-2 (IL-2) immunotherapy less toxic and more effective against cancer. In doing so, the team has uncovered surprising new information about how to boost the antitumour activity of interleukin-2 molecules.
IL-2 has been in clinical use for decades, and has been called ‘the first effective cancer immunotherapy’. But, it is so toxic that it is currently only prescribed in a very limited number of late-stage cancers.
Associate Professor Daniel Christ, who led the research, said that IL-2’s potential to be a better anticancer therapy is promising.
“We are currently witnessing an explosion in new immunotherapies for cancer, such as the immune checkpoint inhibitors – and this has really reinvigorated huge interest in early immunotherapies, such as IL-2, that can support the immune system to attack cancer.”
“Importantly, we’re seeing that immunotherapies tend to work better in combination – so one reason we wanted to investigate IL-2 again was because it could be a good candidate for use in combination therapy with newer treatments.”
In the current study the research team set out to make a range of different versions of IL-2.
“We wanted to make two key changes to IL-2,” said Dr Rodrigo Vazquez-Lombardi, who co-led the research with A/Prof Christ and Professor Jonathan Sprent.
“We wanted to make it more powerful as an antitumour agent, and we also wanted to extend its half-life in the body – because IL-2 is removed from the blood so rapidly that this limits its use as a therapy. We reasoned that, by doing both things, we had a good chance of developing a more effective and less toxic version.”
IL-2 acts against cancer by instructing immune cells on how to behave towards a tumour. In particular, IL-2 activates ‘killer cells’, such as killer T cells and natural killer cells, stimulating them to attack tumours.
When the researchers looked more closely, they found that modifying the IL-2 molecules changed their behaviour and helped to reduce the numbers of a different class of immune cell – the regulatory T cells. These cells are a part of the immune system that suppress immune responses of other cells.
The researchers say their findings will change thinking about IL-2, and provide important guidance for the development of future IL-2-based therapies.
Prof Sprent points out, “Clinicians have become wary of IL-2 therapy for cancer because it’s a double-edged sword: the benefits of boosting killer cell function are countered by the parallel stimulation of T regulatory cells.
“Our simple trick of selectively stimulating just the killer cells and not the T regulatory cells is a real breakthrough and should restore faith in IL-2 therapy.”
Their findings were recently published in Nature Communications.
The original post was published on Garvan’s website. Image of Dr Rodrigo Vazquez-Lombardi courtesy of Garvan.
ACRF has supported cancer research at Garvan by providing three grants, totalling AUD $6.13million, towards cutting edge cancer research infrastructure, equipment and technology.
Image: Dr Rodrigo Vazquez-Lombardi