Solving the IL-15 Problem

There’s a secret weapon that can help your body fight cancer: Interleukin 15, otherwise known as IL-15.

This powerful cytokine activates your immune cells—particularly natural killer (NK) cells—and fires them up to identify and kill cancer cells.

The problem? Cancer cells have developed some insidious strategies to suppress the activity of NK cells, and levels of IL-15 are often too low to activate NK cells effectively.

Unfortunately, simply delivering IL-15-based drugs to cancer patients is much like using a sledgehammer to crack a walnut: it activates NK cells throughout the body rather than within the tumor alone, resulting in severe toxicity.

The hope of using IL-15 to effectively treat cancer without causing extreme side effects seemed impossible, and very few biotechs have even attempted to pursue this bold target.

But not us.

At Audax we welcome a challenge, and our team of immuno-oncology experts and biotech thought leaders became obsessive about solving the IL-15 problem.

Now, we can say we’ve achieved the impossible.

In collaboration with the Monash Biomedicine Discovery Institute, the Audax team have identified a strategy to make NK cells ultra-sensitive to low levels of IL-15 that naturally occur in solid tumors, an approach that could revolutionize the treatment of such cancers.

Led by our Chief Technology Officer, Iva Nikolic, and Vice President of Computational Biology, Joe Cursons, our team used our advanced CRISPR screening platform to identify genes that can be deleted to supercharge NK cells.

The gene we identified can be switched off using different methods: small molecule drugs can be used to inhibit the enzyme it codes for, and it can also be deleted in cell therapies.

We’ve put this drug target to the test in preclinical models of colorectal cancer, which typically has high rates of tumor recurrence and poor patient outcomes. Our approach results in powerful immune activation at the tumor site, while preventing damage to other organs. It’s an incredible breakthrough for cancer drug development and the treatment of solid tumors.

And that’s not all. Making NK cells ultra-sensitive to IL-15 can be used in combination with current gold-standard cancer treatments, such as immune checkpoint inhibitors, in order to further improve patient outcomes.

Read about how we achieved this feat in our new paper published in Cancer Cell and follow us as we develop this new biology into a potential new cancer treatment.

“I’m extremely proud of the team for publishing this exciting example of the research we perform here at oNKo,” said Jai Rautela, co-founder and CEO of Audax. “The work typifies the dynamism and thought leadership that comes from our multi-talented group, being united around the common goal of deeply understanding immunobiology. It really validates our vision to create medicines from foundational immunology research.”

Full article in Cancer Cell