Nuo Xu et al developed new approaches to enhance the efficiency of chimeric antigen receptor T cells (CAR T) therapy in solid tumours. The CAR T therapy, which is used for treating blood cancers, has been found less effective against solid tumours as the cells and molecules surrounding tumours were often immunosuppressive, activating an immune checkpoint that causes the CAR T cells to lose their activity. The team found that treating the mice models with cGAMP that activate the antimicrobial immune cell signalling STING pathway created a proinflammatory environment within the mouse tumours. This improved the CAR T cells’ ability to accumulate and attack tumour cells.
The accumulation was particularly great when the mice were infused with CAR T cells that produced the immune signalling molecule IL-17A.
The team noted that CAR T cell attack could be sustained for longer periods when treated with 5,6-dimethylxanthenone-4-acetic acid (DMXAA). DMXAA depleted immunosuppressive cells from the tumour environment and prevented the immune checkpoint from deactivating the CAR T cells. The researchers found that combining these approaches with the addition of anti–PD-1 and anti–GR-1 mAb led to sustained tumour regression.
Source: Journal of Experimental Medicine (2021)| 218 (2): e20200844| https://doi.org/10.1084/jem.20200844