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STING agonist promotes CAR T cell trafficking and persistence in breast cancer
Xu, N., Palmer, D., Robeson, A., Shou, P., Bommiasamy, H., Laurie, S., Willis, C. D., Dotti, G., Vincent, B. G., Restifo, N. P., & Serody, J. (2021). STING agonist promotes CAR T cell trafficking and persistence in breast cancer. Journal of Experimental Medicine.
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 CAR T 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 CAR T 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.
