Innovative dual-target drug may lead to new investigational approach for breast cancer patients

Researchers, led by the University of Melbourne’s Professor Laura Mackay, a Laboratory Head and Immunology Theme Leader at the Peter Doherty Institute of Infection and Immunity (Doherty Institute), in collaboration with Pfizer, have discovered new insights into possible future treatments for breast cancer.  

A new dual-target drug that has been shown to supercharge cancer-fighting immune cells in mice may support a new treatment approach for patients, potentially paving the way for improved outcomes in breast cancer care. 

Breast cancer is the fifth most common cause of cancer death in Australia, with more than 20,000 Australians diagnosed per year. Over 1,000 of those diagnosed are young Australian women under 40. There is an urgent need to discover more effective treatments for breast cancer.  

Immunotherapy represents one of the most promising new treatments for cancer, by boosting the body’s own immune cells to kill cancer cells. However, only a small proportion of breast cancer patients respond to existing immunotherapy treatments.  

Results from a new study published in Clinical and Translational Immunology found that dual-target antibody therapy can enhance cancer-fighting T cells more effectively than current single-target therapy in mice. Professor Mackay explained the importance of this research for cancer patients. 

“We need to find new ways to instruct the immune system to fight cancer,” said Professor Mackay. 

“Our research shows that a two-pronged strategy can better ignite cancer-fighting immune cells, which is the goal of immunotherapy.” 

Some cancer cells are coated with proteins that allow them to hide from immune cells and continue to grow. In a research collaboration with Pfizer Inc. two such proteins, CD47 and PD-L1, were ‘unmasked’, exposing the cancer cells to the immune system for destruction.    

While therapies targeting CD47 and PD-L1 have been tested individually, they both present limitations such as toxicity to patients or poor response rates. Therefore, dual-target antibody therapy that can maximise their anti-cancer functions while minimising these obstacles was explored.  

Lead author of the study, the University of Melbourne’s Dr Susan Christo, Senior Research Officer at the Doherty Institute, described how this research may influence treatment approaches for breast cancer patients in the future. 

“The idea that cancer-fighting immune cells can gain more power when we target multiple key proteins at once may be a real game-changer in the field of immunotherapy,” said Dr Christo. 

“Our work opens up new opportunities to explore how different combinations of drugs can supercharge the immune system to beat cancer. 

“The advantage of a dual-target approach is that it can be used for a wide range of solid cancers. This means that more patients could benefit from its anti-cancer function, inspiring us to do more research with the hopes of going to clinical trials.” 

This research study was made possible with thanks to funding from Pfizer Inc. and the National Health and Medical Research Council (NHMRC). 

#END#

Additional information: 

• Peer reviewed paper: Christo S, et al. Dual CD47 and PD‐L1 blockade elicits anti‐tumor immunity by intratumoral CD8+ T cells. Clinical & Translational Immunology (2024). DOI: https://doi.org/10.1002/cti2.70014  

• Funding: This work was supported by Pfizer Inc. and the National Health and Medical Research Council (NHMRC). 

• Collaboration: This study is the result of a collaborative effort between the Doherty Institute and Pfizer. 

Relevant Australian breast cancer statistics: 

• Breast cancer is the most common cancer in Australian women and the second most common cancer overall. 

• In 2024, an estimated 21,194 Australians (20,973 women and 221 men) will have been diagnosed with breast cancer​. 

• Breast cancer is the fifth most common cause of cancer death in Australia. 

• Over 3,300 Australians (3,272 women and 36 men) are expected to die from breast cancer in 2024. This translates to about 9 deaths per day. 

• Approximately 1,000 women under the age of 40 are diagnosed with breast cancer annually​. 

Source: https://www.canceraustralia.gov.au/cancer-types/breast-cancer/statistics 

--------------------

Professor Laura Mackay is a Laboratory Head and Immunology Theme Leader at The Doherty Institute. Laura is a Howard Hughes Medical Institute (HHMI) and Bill & Melinda Gates International Scholar, a Dame Kate Campbell Fellow, a Sylvia & Charles Viertel Charitable Foundation Senior Medical Research Fellow, a National Health and Medical Research Council (NHMRC) Leadership Fellow, and in 2022 was the youngest ever Fellow elected to the Australian Academy of Health and Medical Sciences. Laura obtained her PhD from The University of Birmingham, U.K. in 2009, before commencing a post-doctoral position with Professor Francis Carbone at The University of Melbourne. In 2016, she established her laboratory at the Doherty Institute. 

Dr Susan Christo is a senior research officer at the Doherty Institute. Dr Susan Christo obtained her PhD at the University of South Australia in 2015 before joining the laboratory of Professor Laura Mackay at the Doherty Institute in 2016. Susan has an interest in T cell biology and is currently working on identifying key factors that regulate the identity and function of tissue T cell in a range of settings such as cancer. Susan’s work hopes to instruct the design of T cell-based immunotherapies aimed at long-term protection in an organ-specific manner.