Harnessing the innate immune system to develop new therapies for Triple Negative Breast Cancer (TNBC)

Project Description 

Immunotherapy has transformed the treatment of some cancers, including advanced melanoma and lung cancer. These treatments work by harnessing the body’s adaptive immune system – the part of our immune defence that learns to recognise threats after we’ve been exposed to infections or received vaccinations.

However, only a small proportion of people with breast cancer benefit from these therapies. Finding ways to improve the response to immunotherapy is a major focus of research, especially for Triple Negative Breast Cancer (TNBC). TNBC is an aggressive type of breast cancer that lacks hormone receptors, which means many of the most effective targeted treatments simply do not work for these patients.

This research project aims to take a different approach. Instead of focusing on the adaptive immune system, it targets the innate immune system – the body’s rapid first line of defence against infection. Associate Professor Tatyana Chtanova from UNSW Sydney and the Garvan Institute of Medical Research has discovered that certain white blood cells, called neutrophils, found within breast tumours can be reprogrammed to attack cancer cells rather than support tumour growth.

By developing new types of immunotherapy that better harness the body’s natural defences, this work aims to create more effective treatment options for people diagnosed with TNBC and ultimately improve patient outcomes.

Why This Work is Needed

TNBC is one of the most aggressive forms of breast cancer with limited treatment options. It also has a high recurrence rate and some of the poorest outcomes, – new therapeutic approaches are desperately needed. Immunotherapy has revolutionised the treatment of some solid cancers such as metastatic melanoma and lung cancer, but only a small proportion of people diagnosed

with breast cancer respond to this treatment. So, there is a great need to develop new immunotherapies that are effective for hard-to-treat breast cancers like TNBC.

Expected Outcomes

Ultimately, the knowledge gained from this study will enable Associate Professor Chtanova to develop and optimise new immunotherapies that target the innate immune system – an alternative approach that could treat tumours more effectively, provide long-term protection against future tumour growth, and improve outcomes for people diagnosed with TNBC who havelimited treatment options.

Project Details

Immunotherapy is showing enormous promise in the treatment of solid cancers such as metastatic melanoma and lung cancer. Unfortunately, current immunotherapies only benefit a small proportion of people diagnosed with breast cancer. In this research project, Associate Professor Tatyana Chtanova and her team will focus on understanding how neutrophils – specialised white blood cells that defend against bacterial infection yet promote tumour growth – can be reprogrammed to destroy TNBC cells. They will then use this new understanding of neutrophils to develop and optimise a new type of immunotherapy that uses bacteria (delivered via drugs that treat bacterial infection) to activate an immune response in neutrophils to convert them into cancer fighters. In previous studies, Associate Professor Chtanova and her team have already shown that this approach can slow tumour growth and improve survival rates in preclinical models of TNBC. The overall goal of this project is to provide the pre-clinical data necessary to optimise and bring these new treatments into the clinic for people diagnosed with TNBC, most of whom do not benefit from currently available immunotherapies.