Engineered PLGA microparticles for long-term, pulsatile release of STING agonist for cancer immunotherapy
Xueguang Lu, Lei Miao, Wenting Gao, Ziqi Chen, Kevin J. McHugh, Yehui Sun, Zachary L. Tochka, Stephanie Tomasic, Kaitlyn Sadtler, Alain Hyacinthe, Yuxuan Huang, Tyler P. Graf, Quanyin Hu, Morteza Sarmadi, Róbert Langer, Daniel G. Anderson, Ana Jaklenec
Abstract
-glycolic acid (PLGA) particles that remain at the site of injection and release encapsulated STING agonist as a programmable sequence of pulses at predetermined time points that mimic multiple injections over days to weeks. A single intratumoral injection of STING agonist-loaded microparticles triggered potent local and systemic antitumor immune responses, inhibited tumor growth, and prolonged survival as effectively as multiple soluble doses, but with reduced metastasis in several mouse tumor models. STING agonist-loaded microparticles improved the response to immune checkpoint blockade therapy and substantially decreased the tumor recurrence rate from 100 to 25% in mouse models of melanoma when administered during surgical resection. In addition, we demonstrated the therapeutic efficacy of STING microparticles on an orthotopic pancreatic cancer model in mice that does not allow multiple intratumoral injections. These findings could directly benefit current STING agonist therapy by decreasing the number of injections, reducing risk of metastasis, and expanding its applicability to hard-to-reach cancers.