Autologous-cancer-cryoablation-mediated nanovaccine augments systematic immunotherapy.

ABSTRACT

Cancer vaccines developed from autologous tumors hold tremendous promise for individualized cancer immunotherapy. Cryoablation-induced in situ autologous antigens are capable of activating systemic immunity with low damage. However, the dissipation of cancer fragments after cryoablation induces poor immunogenicity and short-time maintenance of immunological memory. To solve this challenge, a nanovaccine with functional grippers is proposed to largely enhance the in situ grasping of tumor fragments, combined with an immune adjuvant to further strengthen the immune-therapeutic effect. Herein, maleimide-modified Pluronic F127-chitosan nanoparticles encapsulating Astragalus polysaccharide (AMNPs) are developed. The AMNPs can capture multifarious and immunogenic tumor antigens generated through cryoablation, specifically target lymph nodes and facilitate lysosome escape to activate remote dendritic cells, and modulate T cell differentiation through cross-presentation, thereby breaking the immunosuppressive microenvironment to achieve durable and robust tumor-specific immunity. In the bilateral Lewis lung cancer tumor model, AMNP-mediated cryoablation can significantly regress primary tumors (with a tumor growth inhibition rate of 100%, and a recurrence rate of 0% (30 days) and 16.67% (60 days)), inhibit untreated abscopal tumor growth (a decrease of about 3.84-fold compared with the saline group), and ultimately improve the long-term survival rate (83.33%). Collectively, the development of a lymph-node-targeted in situ cancer-cryoablation-mediated nanovaccine provides a promising approach for personalized cancer immunotherapy against metastatic cancers.