Vaccinations for Triple-Negative and Brain Metastatic Breast Cancer

Project Description: Triple negative and brain-metastatic breast cancer remain two of the most challenging subtypes to treat, as they are not responsive to currently available chemotherapy treatments. Dr Roberta Mazzieri (The University of Queensland) hopes to address this with a new vaccination-based technology to generate anti-tumour immune responses within the body.

Why this work is needed: Standard chemotherapy has been shown to have poor efficacy in certain challenging breast cancer subtypes, such as triple negative breast cancer (TNBC), or cancer which spreads to the brain. Hence, new options are urgently needed to help women with these treatment-resistant diseases.

Expected outcomes: This study will test the efficacy of a series of new cancer vaccines, which can modulate the patient’s own immune cells to better recognise and eliminate cancer cells with the potential to enhance the response when used in combination with other immunotherapies. The experiments will be performed as a prelude to early-phase human clinical trials, and will actively involve the input of patients and clinicians.

Project details

Triple-negative and brain metastatic disease are manifestations of breast cancer that remain a great challenge for patients and their doctors. They are not sensitive to the molecular-targeted drugs used to treat other types of breast cancer (e.g. hormone therapy and HER2-targeting drugs), and account for a significant fraction of the morbidity and mortality of breast cancer.

Immunotherapy, which targets the body’s own natural defenses to fight the cancer, has shown great promise in many cancer types, but is not as effective in breast cancer. To address this problem, Dr Mazzieri and her team have developed a new vaccination-based technology that specifically stimulates the immune cells, helping to boost their response to immunotherapy in breast cancer.

The team have identified a number of potential vaccine targets, and will now test these in a specialised mouse model of breast cancer. This mouse model has been modified to add a functional “humanised” immune system. This will allow assessment of the therapeutic efficacy of the new vaccines, including when they are used in combination with other immunotherapies. We will also verify whether immune responses to the new immunotherapeutic targets are present in the blood of breast cancer patients. This will validate them as clinically relevant targets for the development of more effective cancer vaccine.

Ultimately, the goal of this study is to identify potential vaccination-based therapies for use in future clinical trials, to improve the prognosis for women with aggressive breast cancer forms.