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.