A vaccine-based nanosystem for initiating innate immunity and improving tumor immunotherapy

Di-Wei Zheng, Fan Gao, Qian Cheng, Peng Bao, Xue Dong, Jin-Xuan Fan, Wen Song, Xuan Zeng, Si-Xue Cheng and Xian-Zheng Zhang ()
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Di-Wei Zheng: Wuhan University
Fan Gao: Wuhan University
Qian Cheng: Wuhan University
Peng Bao: Wuhan University
Xue Dong: Wuhan University
Jin-Xuan Fan: Wuhan University
Wen Song: Wuhan University
Xuan Zeng: Wuhan University
Si-Xue Cheng: Wuhan University
Xian-Zheng Zhang: Wuhan University

Nature Communications, 2020, vol. 11, issue 1, 1-15

Abstract: Abstract The unsatisfactory response rate of immune checkpoint blockade (ICB) immunotherapy severely limits its clinical application as a tumor therapy. Here, we generate a vaccine-based nanosystem by integrating siRNA for Cd274 into the commercial human papillomavirus (HPV) L1 (HPV16 L1) protein. This nanosystem has good biosafety and enhances the therapeutic response rate of anti-tumor immunotherapy. The HPV16 L1 protein activates innate immunity through the type I interferon pathway and exhibits an efficient anti-cancer effect when cooperating with ICB therapy. For both resectable and unresectable breast tumors, the nanosystem decreases 71% tumor recurrence and extends progression-free survival by 67%. Most importantly, the nanosystem successfully induces high response rates in various genetically modified breast cancer models with different antigen loads. The strong immune stimulation elicited by this vaccine-based nanosystem might constitute an approach to significantly improve current ICB immunotherapy.

Date: 2020
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DOI: 10.1038/s41467-020-15927-0

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