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bioRxiv · 10.1101/2025.02.09.636745

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.
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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.

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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.. 2025-02-11. In situ generated vaccine-like pyroptosome for personalized cancer immunotherapy. https://doi.org/10.1101/2025.02.09.636745

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