STING agonist promotes CAR T cell trafficking and in breast cancer

CAR T therapy targeting solid tumors is restrained by limited infiltration and persistence of those cells in the tumor microenvironment (TME). Here, we developed approaches to enhance the activity of CAR T cells using an orthotopic model of locally advanced breast cancer. CAR T cells generated from Th/Tc17 cells given with the STING agonists DMXAA or cGAMP greatly enhanced tumor control, which was associated with enhanced CART cell persistence in the TME. Using single-cell RNA sequencing, we demonstrate that DMXAA promoted CAR T cell trafficking and persistence, supported by the generation of a chemokine milieu that promoted CART cell recruitment and modulation of the immunosuppressive TME through alterations in the balance of immune-stimulatory and suppressive myeloid cells. However, sustained tumor regression was accomplished only with the addition of anti-PD-1 and anti-GR-1 mAb to Th/Tc17 CAR T cell therapy given with STING agonists. This study provides new approaches to enhance adoptive T cell therapy in solid tumors.

Automated summary

The study demonstrates that enhancing CAR T cell therapy targeting solid tumors with STING agonists, specifically DMXAA, can greatly improve tumor control by promoting CAR T cell trafficking and persistence in the tumor microenvironment. The single-cell RNA sequencing results show that DMXAA generates a chemokine milieu that facilitates CART cell recruitment and modulates the immunosuppressive TME.