Controlling cancer-induced inflammation with a nucleic acid scavenger prevents lung metastasis in murine models of breast cancer.
Tumor cells release nucleic acid-containing pro-inflammatory complexes, termed Nucleic Acid-containing Damage-Associated Molecular Patterns (NA DAMPs), passively upon death and actively during stress. NA DAMPs activate pattern recognition receptors on cells in the tumor microenvironment leading to prolonged and intensified inflammation that potentiates metastasis. No strategy exists to control endogenous or therapy-induced inflammation in cancer patients. We discovered that the polyamidoamine dendrimer PAMAM-G3 scavenges NA DAMPs and mitigates their pro-inflammatory effects. In this study we tested if the nucleic acid scavenger (NAS) PAMAM-G3 reduces lung metastasis in murine models of breast cancer. Our data indicate that PAMAM-G3 treatment decreases cell-free DNA levels and reduces lung metastasis in the experimental intravenous tumor injection model and the post-surgical tumor resection model of 4T1 breast cancer. Reduction in lung metastasis is associated with reduction in inflammatory immune cell subsets and pro-inflammatory cytokine levels in the tumor and the periphery. This study is the first example of NAS-mediated inhibition of metastasis to the lung. The study results provide a strong rationale for inclusion of NAS therapy in women with breast cancer undergoing standard-of-care surgery.
Holl, Eda, Victoria Frazier, Karenia Landa, David Boczkowski, Bruce Sullenger, and Smita K. Nair. “Controlling cancer-induced inflammation with a nucleic acid scavenger prevents lung metastasis in murine models of breast cancer.” Mol Ther, December 18, 2020. https://doi.org/10.1016/j.ymthe.2020.12.026.