Accelerating the discovery of novel cancer therapies

Immunotherapy is now often regarded as the preferred course of action when it comes to cancer treatment.

Different to traditional therapies such as chemotherapy and radiation therapy, which target the cancer itself, immunotherapies harness the patients' own immune system to fight cancer cells.

Because immune cells – and specifically T cells, a subtype of white blood cells – can recognise infected cells or tumors, they have the ability to slow or destroy them.

“T cells are one of the body’s best weapons to protect against infection and cancerous tumours,” says University of Melbourne Immunologist Professor Laura Mackay.

Immunotherapy: blood v tissue T cells

Cancer immunotherapies that target T cells currently focus on T cells in the blood. While there are two main types of this T cell therapy – tumor-infiltrating lymphocytes therapy and CAR T-cell therapy – both involve modifying T cells so that they are better equipped to fight cancer.

For blood cancers, like leukemia, T cell therapies have been very effective. But for solid cancers of the tissue, such as breast or melanoma, the benefits lessen. To fight those cancers, tissue-resident memory T cells (TRM cells) may be key.

“Targeting T cells in the tissue itself provides more effective immune protection,” says Professor Mackay.

“In other words, T cells kill cancer. Tissue resident T cells do it even better.”

This is not as simple as it sounds.

As well as a multitude of variables – including that some tissue micro-environments have an effect on how T cells can do their job, it’s also about timing, that is, whether T cells in the tissue (or tumour) are already at the right place at the right time. Simply put, T cells in tissue are simply different to those in blood, and less is known about the former.

“It’s increasingly apparent that immune cells are the key to developing better oncology treatments,” Professor Mackay says. “But we need to better understand T cells – and specifically TRM cells – to get the most out of them.”

At the forefront of immunotherapy research

This is what Professor Mackay is working on, and which Pfizer has recently invested in through a three-year partnership with the University of Melbourne to support her research.

Conducted from the Department of Immunology and Microbiology at the Doherty Institute, the ‘Targeting Tissue Resident Immune Cells for Cancer Immunotherapy’ project aims to identify ways to augment tissue-resident T cell formation and function to provide enhanced local immunity, as well as how they can be utilised for next generation vaccines.

“We're looking at how we can engineer more of these TRM cells to fight cancer more effectively. The hope is to find ways to target the cells so they can make vaccines that incorporate them into new treatments.”

Professor Mackay has been looking at T cells for over 15 years, having an interest in the immune system since she had glandular fever as a teenager.

Since 2009, her focus has been on the difference between blood T cells and tissue T cells in protecting against infection. Over the decade that followed, it was Professor Mackay and her team who showed that the TRM cells are better at protecting against infection and tumors.

For the development of new immunotherapeutic strategies against disease, this discovery is key. It has driven a new field of T cell immunology and put Professor Mackay’s work at the forefront of research into immunotherapy resulting in Awards including the Australian Academy of Science's Gottschalk Medal and the Prime Minister’s Prize for Life Scientist of the Year.

Pfizer recognised this. And this project builds on her considerable body of immunotherapy research.

Accelerating discovery through partnerships

While the long-term goal is to develop better treatments for cancer immunotherapy, the aim of the partnership is primarily discovery.

“They’re funding research,” says Professor Mackay. “While we are still in the early stages of target identification, Pfizer appreciate we are onto something that is going to be key to new treatments.”

At a time when the Australian government is focused on funding highly translational research, and usually pharmaceutical companies only provide funding when there is therapeutic ready to go, this is significant. It also highlights the importance of this discovery stage.

“Any major therapeutic achievements require discovery research,” notes Professor Mackay. “Just look at COVID-19 vaccines. We could make the MRNA vaccine so fast because years ago they were putting money into basic biology. You can’t have one without the other.”

Anand Gautam, Executive Director & Emerging Science Lead at Pfizer, agrees.

“It is Pfizer’s purpose to bring breakthroughs that change patients’ lives. We are committed to investing in novel and cutting-edge emerging science to develop novel therapeutics. Professor Laura Mackay is one of the most recognised and respected immunologists in the world, driving the field of tissue resident immunity (TRM).

“She is well placed to identify new modes of action and targets in TRMs that could potentially lead to new therapeutics to treat cancer and other chronic diseases. We are encouraged to see the pioneering work being done in cancer immunotherapy and through this collaboration, hope to accelerate the discovery of potential novel therapies for cancers.”

The partnership will of course accelerate the path to tangible treatments. As well as funding, Pfizer provides access to frontline therapeutics, scientific analysis, and the ability to test findings with existing treatments for compatibility. Professor Mackay can progress her research much faster.

But at this stage, the focus remains on discovery. “All findings – positive and negative – are important because we need to find out what works,”  Professor Mackay says.

“My hope for the future is that our research will have translated into better treatments for patients suffering from a range of diseases – cancer, as well as malaria and influenza for example.

"By collaborating with the teams at Pfizer, we can really speed that up and we might be able to make a difference in our lifetime. That helps everyone.”