Developing a new CAR T-cell therapy to target Triple Negative Breast Cancer (TNBC) that has spread to the brain

Professor Kum Kum Khanna is Group Leader of the Tumour Biology and Therapeutics Research Group at the Mater Research Institute, The University of Queensland.

The challenge:

Triple Negative Breast Cancer (TNBC) is one of the most aggressive forms of breast cancer. It often affects younger women and is difficult to treat because it lacks the common hormone or growth factor receptors that many existing breast cancer treatments target, leaving fewer treatment options. A particularly serious clinical problem occurs when TNBC spreads (metastasises) to the brain. Once this happens, treatment options are very limited because most drugs cannot cross the blood–brain barrier, a natural defence that protects the brain. As a result, outcomes for people with TNBC brain metastases are poor.

A recently approved drug, sacituzumab govitecan, targets a protein called Trop2, which is commonly found at high levels on TNBC cells. While this drug has been shown to be effective for some people with advanced TNBC, it has shown little benefit for people whose cancer has spread to the brain. This highlights the urgent need for new treatments that can both reach the brain and effectively destroy cancer cells there.

Project description:

Professor Kum Kum Khanna’s Pink Sky Grant project, funded by the National Breast Cancer Foundation (NBCF), aims to develop a new type of immunotherapy using Chimeric Antigen Receptor (CAR) T-cell technology. CAR T-cell therapy involves collecting a person’s own immune cells (T cells) and modifying them in the laboratory so they can recognise and attack cancer cells.

Professor Khanna and her team are using a type of T cell that naturally recognises human cytomegalovirus (CMV), a common virus that most adults have been exposed to. These CMV‑specific T cells are long‑lasting, powerful immune cells and are particularly good at travelling into the brain. Previous early clinical studies led by the research team have shown that CMV‑specific T cells can be used safely in people with brain cancers, making them a promising platform for treating breast cancer that has spread to the brain.

The research team has engineered advanced CMV-specific CAR T cells to recognise Trop2, a protein found on most on TNBC cells. They have also incorporated additional internal signalling components designed to improve the cells’ ability to survive, multiply and kill cancer cells. Early laboratory studies have shown that these engineered CMV-specific CAR T cells can effectively target and kill Trop2-positive cancer cells while sparing healthy cells.

This project will test the therapy in advanced human-derived preclinical models to assess how effectively the CAR T cells can reach tumours in the brain, kill cancer cells and do so safely, generating critical evidence needed to support future clinical trials for people with metastatic TNBC.

Potential impact:

If successful, Professor Khanna’s Pink Sky Grant project could lead to the first CAR T-cell therapy specifically designed for TNBC that has spread to the brain. By generating the evidence needed to move towards clinical trials, this project could open a new treatment pathway for people who currently have very few effective treatment options.

A therapy that can cross the blood–brain barrier and precisely target cancer cells has the potential to reduce deaths, improve survival, reduce treatment side effects, and offer a more personalised approach to care. Beyond TNBC, this work could also pave the way for similar treatments for other cancers that spread to the brain, supporting future breakthroughs in cancer immunotherapy.

Grant code: 2025/PS0080
Active years: 2026-2029
Scientific project title: Trop2 CAR T-cell immunotherapy for brain-metastases in Triple-Negative Breast Cancer