Immunotherapy with BiTE: Armouring CAR T cells against breast cancer

Dr Yu-Kuan (Tony) Huang is a Cancer Immunologist based in the Paul Beavis Lab at the Peter MacCallum Cancer Centre.

The challenge:

Immunotherapy has transformed treatment for some cancers, but achieving the same success in breast cancer has been much more challenging. Two promising approaches, Chimeric Antigen Receptor (CAR) T-cell therapy and Bispecific T-Cell Engagers (BiTEs), can direct immune cells to recognise and kill cancer cells, but their success in treating solid tumours has been limited.

Solid tumours create a hostile environment that makes it hard for immune cells to enter, survive and remain active. Cancer cells within the same tumour can also be diverse, meaning a single target (antigen) may not be present on all cells. Some targets may also be present at low levels on healthy tissues, increasing the risk of side effects. Together, these challenges restrict which tumour markers can be targeted safely and limit who can benefit from immunotherapy.

Project description:

Dr Yu-Kuan (Tony) Huang’s Pink Sky Grant project, funded by the National Breast Cancer Foundation (NBCF), aims to overcome these barriers by engineering ‘armoured’ CAR T cells. CAR T-cell therapy involves collecting a person’s own immune cells (T cells) and modifying them in the lab so they can recognise and attack cancer cells. Armoured CAR-T cells are designed to attack a tumour target while also producing immune-activating molecules, called BiTEs, directly within the tumour. The BiTEs help recruit and activate both the engineered CAR T cells and the person’s own immune cells, enabling them to recognise and attack a broader range of cancer cells within the tumour.

Using a CRISPR-based gene-editing system, the team will ensure that BiTEs are produced only when the CAR T cells are inside the tumour. This localised approach is intended to strengthen anti-cancer immune responses while reducing the risk of damage to healthy tissues.

The project will focus on BiTEs targeting HER2, a well-known protein often found at high levels in breast cancer cells, and EpCAM, a marker present on many cancers but also found in some healthy tissues. By restricting BiTE activity to the tumour site, the researchers aim to safely target a broader range of cancer markers that would otherwise be difficult to target without causing side effects.

Potential impact:

If successful, Dr Huang’s Pink Sky Grant project could improve how immunotherapy is applied in breast cancer. It could increase treatment effectiveness, reduce side effects and expand the number of people who may benefit from immunotherapy. In the longer term, this approach could be adapted for other solid cancers, supporting broader advances in cancer immunotherapy.

Grant code: 2025/PS0060
Active years: 2026-2029
Scientific project title: Armouring CAR T cells with a tumour-localised bi-specific T cell engager for treating breast cancer