In situ-generated vaccine-like pyroptosome for personalized cancer immunotherapy

The efficacy of in situ cancer vaccination has been hampered by a poor spatiotemporal orchestration of multiple key steps of the cancer-immunity cycle in most tumours and systemic toxicity related to therapeutic strategies. Here we report a systemic injectable and pyroptosis-enabled nanoadjuvant that evokes the secretion of a vaccine-like pyroptosome in the tumour area for robust antitumour immunity. This systemic injectable and pyroptosis-enabled nanoadjuvant induces vigorous immunogenic pyroptosis, triggering the efficient release of tumour antigen-rich pyroptosomes, damage-associated molecular patterns and proinflammatory cytokines. Photoactivatable release of a TLR7/8 agonist into the pyroptosome generates an in situ cancer vaccine platform that cooperatively activates the cancer-immunity cycle and avoids systemic toxicity. The vaccine boosts both innate and adaptive immune responses, facilitating the eradication of primary tumours and metastatic nodules, thereby providing long-lasting cancer prevention. Overall, the rational design of pyroptosis-inducing nanomedicines for boosting the cancer-immunity cycle reported here might aid in the development of more efficient personalized cancer immunotherapy approaches.