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In situ generated vaccine-like pyroptosome for personalized cancer immunotherapy

Chen, B.; Wan, F.; Xia, H.; Pan, X.; Wang, L.; Wang, Y.; Yan, Y.; Liu, J.; Tang, M.; Yang, Y.; Qin, M.; Ren, J.; Zhong, L.; Chen, W.; Zhang, Q.; Wang, Y.

2025-02-11 cancer biology
10.1101/2025.02.09.636745 bioRxiv
Show 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.

Published in Nature Materials (predicted rank #5) · training set

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