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A nanovaccine for antigen self-presentation and immunosuppression reversal as a personalized cancer immunotherapy strategy

Abstract

The strategy of combining a vaccine with immune checkpoint inhibitors has been widely investigated in cancer management, but the complete response rate for this strategy is still unresolved. We describe a genetically engineered cell membrane nanovesicle that integrates antigen self-presentation and immunosuppression reversal (ASPIRE) for cancer immunotherapy. The ASPIRE nanovaccine is derived from recombinant adenovirus-infected dendritic cells in which specific peptide-major histocompatibility complex class I (pMHC-I), anti-PD1 antibody and B7 co-stimulatory molecules are simultaneously anchored by a programmed process. ASPIRE can markedly improve antigen delivery to lymphoid organs and generate broad-spectrum T-cell responses that eliminate established tumours. This work presents a powerful vaccine formula that can directly activate both native T cells and exhausted T cells, and suggests a general strategy for personalized cancer immunotherapy.

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Fig. 1: Generation and characterization of DCNV-rAd-Ag.
Fig. 2: DCNV-rAd-Ag for antigen self-presentation and LN targeting.
Fig. 3: DCNV-rAd-Ag for the elicitation of CTL responses.
Fig. 4: ASPIRE vaccine improves the antitumour effect.
Fig. 5: B7 co-stimulation enhances the anti-PD1-based immunosuppression reversal.
Fig. 6: ASPIRE vaccine enhances immunotherapy by integrating antigen self-presentation and immunosuppression reversal, and induces cascade immune responses in heterogeneous tumours.

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Data availability

The authors declare that data supporting the findings of this study are available within the article and its Supplementary Information. All the relevant data can be provided by the authors upon reasonable request

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Acknowledgements

This work was supported by the Major State Basic Research Development Program of China (2017YFA0205201) (G.L.), the National Natural Science Foundation of China (81925019, 81422023 and U1705281) (G.L.), the National University of Singapore Startup Fund (NUHSRO/2020/133/Startup/08) (X.C.), the Nanomedicine Translational Research Programme (NUHSRO/2021/034/TRP/09/Nanomedicine) (X.C.), the Fundamental Research Funds for the Central Universities (20720190088 and 20720200019) (G.L.), the China Postdoctoral Science Foundation (2021M702738) (C.L.) and (2021M700115) (Xue Liu) and the Program for New Century Excellent Talents in University, China (NCET-13-0502) (G.L.).

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Contributions

C.L. and G.L. conceived and designed the experiments. C.L., Xue Liu, X.X., X.P., S.C., L.Z. and X.W. performed the experiments. C.L., Xue Liu, Xuan Liu, Y.Z., E.R., P.L., X.C. and G.L. analysed the data. C.L., Xue Liu, X.C. and G.L. wrote the manuscript. G.L. supervised the entire project. All the authors discussed the results and edited the manuscript.

Corresponding authors

Correspondence to Xiaoyuan Chen or Gang Liu.

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Competing interests

G.L. and C.L. are inventors on a patent (No. ZL202010070724.9) related to this study. The other authors declare no competing interests.

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Nature Nanotechnology thanks Michele De Palma, Lana Kandalaft and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Liu, C., Liu, X., Xiang, X. et al. A nanovaccine for antigen self-presentation and immunosuppression reversal as a personalized cancer immunotherapy strategy. Nat. Nanotechnol. 17, 531–540 (2022). https://doi.org/10.1038/s41565-022-01098-0

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