CAR T- cell therapy for breast cancer is on the cards

CAR T-cell immunotherapy has proven to be the most successful treatment for B-cell leukaemia and lymphoma patients, but extending its benefits to solid tumours such as breast cancer has remained a significant challenge. Unlike non-solid malignancies where CAR T cells can effectively target the bone marrow and lymphatic system, solid tumours present a hostile microenvironment that prevents infused T cells from persisting and expanding at the tumour site, even when they do manage to migrate there. Jonathan S. Serody, MD, the Elizabeth Thomas Professor of Medicine, Microbiology, and Immunology and director of UNC Lineberger's Immunotherapy Program, noted that while CAR T cells have been shown to be safe for patients with solid tumours, they have not been able to cause significant tumour regression in the vast majority of treated patients, making the development of new strategies to improve their effectiveness a critical area of research.

Researchers at the UNC Lineberger Comprehensive Cancer Center focused their efforts on Th17 and Tc17 cells, which demonstrate superior survival capacities and have been shown to persist longer in the tumour microenvironment, using two small compounds known as STING agonists — DMXAA and cGAMP — to promote their accumulation around solid tumours. While DMXAA performed well in mouse models, it failed to show benefit in human clinical trials because it does not activate human STING, whereas cGAMP activates human STING, has been shown to improve human immunity, and is also effective in mice. In Serody's experiments, mice injected with cGAMP showed increased T cell proliferation and migration to the tumour location, resulting in significantly slowed tumour growth and improved survival, findings published in the Journal of Experimental Medicine that researchers believe could be a game-changer for cancer therapy targeting a large variety of solid tumour diseases.