Editors' ChoicePharmacology

A therapy that STINGs tumors

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Sci. Signal.  21 Apr 2015:
Vol. 8, Issue 373, pp. ec104
DOI: 10.1126/scisignal.aab3640

Stimulator of interferon genes (STING) is a receptor found in various cell types and activates an immune response in response to cyclic dinucleotides. Fu et al. found that combining cyclic dinucleotides with a cellular cancer vaccine called STINGVAX was effective against multiple types of tumors in mouse models. Modifying the cyclic dinucleotides to strengthen their binding to human STING increased their antitumor activity. Treatment with STINGVAX caused cancer cells to increase the amount of PD-L1, a protein that suppresses the immune response. Inhibiting the PD-L1 pathway in mice treated with STINGVAX was very effective at killing even poorly immunogenic tumors.

J. Fu, D. B. Kanne, M. Leong, L. H. Glickman, S. M. McWhirter, E. Lemmens, K. Mechette, J. J. Leong, P. Lauer, W. Liu, K. E. Sivick, Q. Zeng, K. C. Soares, L. Zheng, D. A. Portnoy, J. J. Woodward, D. M. Pardoll, T. W. Dubensky Jr., Y. Kim, STING agonist formulated cancer vaccines can cure established tumors resistant to PD-1 blockade. Sci. Transl. Med. 7, 283ra52 (2015). [Abstract]