CARving a path to progress: Innovative CAR T cell immunotherapy for breast cancer

Project Description:

Chimeric antigen receptor (CAR) T therapy is a type of immunotherapy, where a patient’s immune cells called T-cells are re-engineered to fight cancer. While successful in the treatment of certain blood cancers, CAR T therapy is yet to show efficacy in the treatment of solid cancers, like breast cancer. In this NBCF-funded study Prof Phillip Darcy and colleagues propose to evaluate an innovative two stage strategy to optimise CAR T therapy for breast cancer. By employing a pioneering manufacturing technique and cutting-edge editing technology, the team aims to produce CAR T cells capable of overcoming the barries currently faced by these cells. These challenges include persistence, exhaustion, and the harsh conditions within tumours, which typically hinder the immune system from effectively destroying cancer cells.

Why is this work needed:

While immunotherapy using a patient’s own genetically engineered CAR T cells has shown impressive anti-tumour effects in certain blood cancers, it has not been as effective in treating solid cancers such as breast cancer. Thus, a new approach is needed to improve the effectiveness of CAR T cells in breast cancer patients.

Expected outcomes:

The successful outcomes of this study will be the development of the next generation CAR T cells. With the use of an innovative manufacturing method along with cutting-edge gene-editing technology it will result in CAR T cells that will overcome the major barriers of poor persistence, exhaustion and the tough environment inside the tumour that usually hinders the immune system from effectively destroying cancer cells.

Project description:

Deaths from breast cancer occur more frequently in tumours that exhibit more aggressive behaviours, those that resist conventional therapies or develop treatment insensitivity,

ultimately resulting in the development of metastatic disease. Relapsing cancer is responsible for all breast cancer deaths. It’s now widely recognised that harnessing and reprogramming the body’s own immune system is a powerful way to target and kill cancer. Chimeric antigen receptor (CAR) T therapy is a type of immunotherapy, where a patient’s immune cells called T-cells are re-engineered to fight cancer. Manipulating a patient’s T-cells by attaching a CAR molecule to recognise and destroy cancer cells has been successful in the treatment of certain blood cancers but has not been effective to date in clinical trials for the treatment of solid tumours like breast cancer. The poor efficacy of CAR T cell therapy in solid tumours is in part due to the low survival of CAR T cells within the tumour site, the suppressive nature of immune cells within the tumour environment, and the exhaustion of CAR T cells.

To address these challenges Prof Phillip Darcy from the University of Melbourne and colleagues propose a novel two stage strategy to optimise CAR T cells therapy. This will involve an innovative manufacturing protocol that generates CAR T cells with enhanced memory and endurance, and state-of-the-art gene-editing technique to increase the anti-tumour function of CAR T cells within the immune suppressive environment of the tumour.

The successful outcome of this novel therapy has the potential to introduce a new paradigm for immunotherapy in solid tumours and lead to improvements in the survival of patients with hard-to-treat metastatic disease.