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Published on: August 1, 2025
In situ-generated vaccine-like pyroptosome for personalized cancer immunotherapy
Binlong Chen1,2, Fangjie Wan3, Heming Xia3
1State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, China. binlong.chen@pku.edu.cn.
Abstract:
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.
Insights
A novel nanoadjuvant enables in situ cancer vaccination by inducing pyroptosis (programmed cell death) and releasing tumor antigens. This approach enhances anti-tumor immunity and prevents recurrence without systemic toxicity.
Area of Science:
- Oncology
- Immunology
- Nanotechnology
- Biomedical Engineering
Background:
- Cancer vaccination efficacy is limited by poor coordination of the cancer-immunity cycle and systemic toxicity.
- Developing effective in situ cancer vaccines requires overcoming these challenges.
Purpose of the Study:
- To develop a systemic injectable, pyroptosis-enabled nanoadjuvant for robust anti-tumor immunity.
- To create an in situ cancer vaccine platform that activates the cancer-immunity cycle and minimizes systemic toxicity.
Main Methods:
- A pyroptosis-inducing nanoadjuvant was designed for systemic injection.
- The nanoadjuvant triggered immunogenic pyroptosis, releasing tumor antigen-rich pyroptosomes.
- A photoactivatable TLR7/8 agonist was incorporated for controlled release within pyroptosomes.
Main Results:
- The nanoadjuvant successfully induced pyroptosis and pyroptosome secretion in the tumor area.
- This process released tumor antigens, damage-associated molecular patterns, and cytokines, activating innate and adaptive immunity.
- The in situ vaccine eradicated primary tumors and metastatic nodules, providing long-lasting protection.
Conclusions:
- Pyroptosis-inducing nanomedicines can effectively boost the cancer-immunity cycle.
- This strategy offers a promising platform for developing efficient, personalized cancer immunotherapies with reduced systemic toxicity.
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