Interventional hydrogel microsphere vaccine as an immune amplifier for activated antitumour immunity after ablation therapy

Xiaoyu Liu, Yaping Zhuang, Wei Huang, Zhuozhuo Wu, Yingjie Chen, Qungang Shan, Yuefang Zhang, Zhiyuan Wu, Xiaoyi Ding, Zilong Qiu, Wenguo Cui () and Zhongmin Wang ()
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Xiaoyu Liu: Ruijin Hospital, Shanghai Jiao Tong University School of Medicine
Yaping Zhuang: Ruijin Hospital, Shanghai Jiao Tong University School of Medicine
Wei Huang: Ruijin Hospital, Shanghai Jiao Tong University School of Medicine
Zhuozhuo Wu: Ruijin Hospital, Shanghai Jiao Tong University School of Medicine
Yingjie Chen: Ruijin Hospital, Shanghai Jiao Tong University School of Medicine
Qungang Shan: Ruijin Hospital, Shanghai Jiao Tong University School of Medicine
Yuefang Zhang: Institute of Neuroscience, CAS Key Laboratory of Primate Neurobiology, State Key Laboratory of Neuroscience, CAS Center for Excellence in Brain Science and Intelligence Technology
Zhiyuan Wu: Ruijin Hospital, Shanghai Jiao Tong University School of Medicine
Xiaoyi Ding: Ruijin Hospital, Shanghai Jiao Tong University School of Medicine
Zilong Qiu: Institute of Neuroscience, CAS Key Laboratory of Primate Neurobiology, State Key Laboratory of Neuroscience, CAS Center for Excellence in Brain Science and Intelligence Technology
Wenguo Cui: Ruijin Hospital, Shanghai Jiao Tong University School of Medicine
Zhongmin Wang: Ruijin Hospital, Shanghai Jiao Tong University School of Medicine

Nature Communications, 2023, vol. 14, issue 1, 1-19

Abstract: Abstract The response rate of pancreatic cancer to chemotherapy or immunotherapy pancreatic cancer is low. Although minimally invasive irreversible electroporation (IRE) ablation is a promising option for irresectable pancreatic cancers, the immunosuppressive tumour microenvironment that characterizes this tumour type enables tumour recurrence. Thus, strengthening endogenous adaptive antitumour immunity is critical for improving the outcome of ablation therapy and post-ablation immune therapy. Here we present a hydrogel microsphere vaccine that amplifies post-ablation anti-cancer immune response via releasing its cargo of FLT3L and CD40L at the relatively lower pH of the tumour bed. The vaccine facilitates migration of the tumour-resident type 1 conventional dendritic cells (cDC1) to the tumour-draining lymph nodes (TdLN), thus initiating the cDC1-mediated antigen cross-presentation cascade, resulting in enhanced endogenous CD8+ T cell response. We show in an orthotopic pancreatic cancer model in male mice that the hydrogel microsphere vaccine transforms the immunologically cold tumour microenvironment into hot in a safe and efficient manner, thus significantly increasing survival and inhibiting the growth of distant metastases.

Date: 2023
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DOI: 10.1038/s41467-023-39759-w

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