Long‐Acting In Situ Cancer Vaccines by Oncolytic STING‐Activating Microgels

In situ cancer vaccines exploiting endogenous multiple antigens directly from tumors to elicit broad immune responses hold great potential in cancer treatment. However, the feeble antigen presentation and hostile immune microenvironments pose severe challenges to acquiring clinical benefits. Here, oncolytic STING‐activating microgels (OSAM) that release oncolytic peptide LTX‐315 and STING adjuvant diABZI in a sustained manner (>4 weeks) have been developed to elicit long‐acting and powerful antitumor immunity. OSAM induced significant upregulation of MHC I and substantial activation of dendritic cells for more than one week. One single intratumoral administration of OSAM markedly promoted the infiltration of cytotoxic T lymphocytes and natural killer cells, which combining with anti‐CTLA‐4 microgels afforded exceptional therapeutic benefits in several different murine tumor models with a cure rate of 40%–71%. These oncolytic STING‐activating microgels introduce a new and powerful strategy to in situ cancer vaccines.