In situ generated vaccine-like pyroptosome for personalized cancer immunotherapy

Abstract The efficacy of in situ cancer vaccination has been hampered by poor spatiotemporal orchestration of multiple key steps of cancer-immunity cycle in most tumours and systemic toxicity related to therapeutic strategies. Here, we report a systemic injectable and pyroptosis-enabled nanoadjuvant (SPEN) that precisely evokes the secretion of vaccine-like pyroptosome in tumour area for eliciting robust anti-tumour immunity. SPEN induces vigorous immunogenic pyroptosis, triggering the efficient release of tumour antigen-rich pyroptosomes, DAMPs, and proinflammatory cytokines. Upon the activatable release of a TLR7/8 agonist into pyroptosome, the generated pyroptosome functions as in situ cancer vaccine for cooperatively activating the cancer-immunity cycle while avoiding systemic toxicity. This in situ vaccine boosts both innate and adaptive immune response, facilitating the eradication of primary tumour and long-lasting cancer prevention. Our findings provide new insights into the rational design of pyroptosis-inducing nanomedicines for boosting the cancer-immunity cycle, thus advancing personalized cancer immunotherapy.