Chemoimmunotherapeutic sealants for postsurgical adjuvant therapy of malignant tumors

Surgery followed by adjuvant therapy is a mainstream clinical strategy for advanced tumors. It is, however, often the case that tumors will recur due to incomplete depletion of residual cancer cells and surgery-triggered immunosuppressive milieu. Herein, we report a chemoimmunotherapeutic fibrin sealant (CI-sealant) as a new postsurgical adjuvant therapy that converts the surgical cavity into an in situ "drug-immune depot" with localized release of immunogenic docetaxel/volasertib dual-drug nanocombo (iNCombo) and galunisertib, a TGF-β inhibitor that relieves immune suppression. The iNCombo elicits strong apoptosis and immunogenic cell death (ICD) in diverse tumor cells, effectively stimulating dendritic cell maturation. CI-sealant induces ICD of residual cancer cells in situ, facilitates T-cell activation and infiltration, and increases the proportion of M1 macrophages, effectively reversing immunosuppression and boosting antitumor immunity in a postoperative 4T1 triple-negative breast cancer model. Post-surgery adjuvant therapy with CI-sealant significantly prevents tumor recurrence in both murine 4T1-Luc breast tumor and B16F10 melanoma models. This chemoimmunotherapeutic sealant opens a promising strategy for postsurgical adjuvant therapy of malignant tumors.