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Potent prophylactic cancer vaccines harnessing surface antigens shared by tumour cells and induced pluripotent stem cells

Nature Biomedical Engineering volume 9, pages 215–233 (2025)Cite this article

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Abstract

The development of prophylactic cancer vaccines typically involves the selection of combinations of tumour-associated antigens, tumour-specific antigens and neoantigens. Here we show that membranes from induced pluripotent stem cells can serve as a tumour-antigen pool, and that a nanoparticle vaccine consisting of self-assembled commercial adjuvants wrapped by such membranes robustly stimulated innate immunity, evaded antigen-specific tolerance and activated B-cell and T-cell responses, which were mediated by epitopes from the abundant number of antigens shared between the membranes of tumour cells and pluripotent stem cells. In mice, the vaccine elicited systemic antitumour memory T-cell and B-cell responses as well as tumour-specific immune responses after a tumour challenge, and inhibited the progression of melanoma, colon cancer, breast cancer and post-operative lung metastases. Harnessing antigens shared by pluripotent stem cell membranes and tumour membranes may facilitate the development of universal cancer vaccines.

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Fig. 1: Enrichment of shared tumour-associated proteins from iPM and the design and characterization of iPM nanovax with membrane antigens and adjuvants.
Fig. 2: In vitro BMDC maturation and T-cell activation stimulation by iPM nanovax.
Fig. 3: In vivo stimulation of systemic immunity and prevention of tumour progression by iPM nanovax.
Fig. 4: Stimulation of potent antitumour T-cell immunity and neoepitope spreading by iPM nanovax.
Fig. 5: Universal cancer prevention by iPM nanovax via the epitopes of shared TAAs existing on iPM.

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Data availability

The RNA-seq data are available from the NCBI database under accession code GSE279478. The mass spectrometry proteomics data are available from the ProteomeXchange Consortium via the PRIDE partner repository with the dataset identifier PXD056678. The raw and analysed datasets generated during the study are available for research purposes from the corresponding authors on reasonable request. Source data are provided with this paper.

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Acknowledgements

We thank the bioinstrumentation platform of the National Center for Nanoscience and Technology for technical support. We also thank W. Qiu, G. Zheng, K. Luo and J. Cui for kind help with the tumour therapy experiments, J. Liang and Y. Wang for detection of the specific T-cell responses in human PBMC samples and A. Sheftel for critical reading of the paper. G.N. discloses support for the research described in this study from the Fundamental Research Center Project of National Natural Science Foundation of China (grant number T2288102) and the Strategic Priority Research Program of the Chinese Academy of Sciences (grant number XDB36000000). R.Z. discloses support for the publication of this study from the National Key Research and Development Program of China (grant number 2023YFC2508500), CAS Project for Young Scientists in Basic Research (grant number YSBR-041) and the Beijing Nova Program (grant number 202304584382). H.Q. discloses support for the publication of this study from the National Natural Science Foundation of China (grant number 32301202). B.H. discloses support for the publication of this study from the National Natural Science Foundation of China (grant number 52473120). H.G. discloses support for the publication of this study from CAMS Innovation Fund for Medical Sciences (grant number CIFMS 2022-I2M-1-009).

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Author notes

  1. These authors contributed equally: Nan Li, Hao Qin, Fei Zhu.

Authors and Affiliations

  1. CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing, P. R. China

    Nan Li, Hao Qin, Fei Zhu, Hao Ding, Yang Chen, Yixuan Lin, Ronghui Deng, Tianyu Ma, Yuanyuan Lv, Changhao Xiong, Rong Li, Yaohua Wei, Jian Shi, Yuliang Zhao, Guangjun Nie & Ruifang Zhao

  2. Center of Materials Science and Optoelectronics Engineering, University of Chinese Academy of Sciences, Beijing, P. R. China

    Nan Li, Yang Chen, Yixuan Lin, Guangjun Nie & Ruifang Zhao

  3. Department of Nutrition and Food Hygiene, School of Public Health, Capital Medical University, Beijing, P. R. China

    Hanqing Chen

  4. School of Chemistry and Chemical Engineering, Guangzhou University, Guangzhou, P. R. China

    Yuliang Zhao

  5. State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, P. R. China

    Guangbiao Zhou, Hua Guo, Mengyao Lv & Yongfang Lin

  6. Department of Orthodontics, Cranial-Facial Growth and Development Center, Peking University School and Hospital of Stomatology, Beijing, P. R. China

    Bing Han

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Contributions

N.L., B.H., G.N. and R.Z. conceived the project. N.L., H.Q. and F.Z. designed and performed most of the experiments, analysed the data and wrote the paper. Y.C. and Yixuan Lin assisted in tumour therapy experiments. T.M. and Y. Lv assisted in obtaining tissue samples and detecting immune responses. H.D., R.D. and C.X. assisted in the data analysis. R.L. and Y.W. assisted in liposome synthesis. J.S. and H.C. provided suggestions on data presentation. G.Z., H.G., M.L. and Yongfang Lin bred the k-Ras muted mice and provided related advice. R.Z. provided suggestions on experiment design and data analysis. B.H., G.N., Y.Z. and R.Z. supervised all experiments. N.L., G.N. and R.Z. wrote and revised the paper.

Corresponding authors

Correspondence to Bing Han, Guangjun Nie or Ruifang Zhao.

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Competing interests

The authors G.N., R.Z. and N.L. are inventors on a filed provisional application for China patent no. CN2024103159244 (An immune composition and its application) and no. CN2024113741833 (Tumour-shared surface antigen epitope peptide and its screening method), submitted by the National Center for Nanoscience and Technology, covering the potential application of tumour prevention of iPM nanovax. The authors declare no other competing interests.

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Nature Biomedical Engineering thanks Siwen Li, Zhuang Liu and the other, anonymous, reviewer(s) for their contribution to the peer review of this work. Peer reviewer reports are available.

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Extended data

Extended Data Fig. 1 Serum antibodies produced by iPM nanovax vaccination against iPSCs and multiple cancer cells.

C57BL6N mice were injected by the indicated groups for totally 4 weeks, once a week. A month later, serum from the indicated groups was incubated with iPSCs (a), MC38 cells (b), or B16F0 cells (c) for 45 min and then stained with anti-IgG, followed by flow cytometry. The data are presented as the mean ± s.d. (n = 6 biological replicates). P values in a–c were calculated using one-way ANOVA with Tukey’s comparison test; ns, no significant difference.

Source data

Extended Data Fig. 2 Increased memory immune responses elicited by iPM nanovax.

The healthy C57BL6N mice received four rounds of iPM nanovax vaccination. Two months later, flow cytometry analysis was performed to determine the percentage of memory B cells and T cells in mice. The frequency of plasma cells (CD3−CD19−CD138−IgM+) in peripheral blood (a) was detected. The percentage of plasma cells (CD3−CD19−CD138−IgM+) and plasmablast cells (CD3−CD19+CD138+IgM+) in bone marrow (b) were detected. The frequency of memory B cells (CD3−CD19+CD138−PDL2+IgM+) in bone marrow (c), central memory T cells (CD44highCD62LhighCD8+ and CD44highCD62LhighCD4+) in peripheral blood (d) and spleen (e) were detected. The data are presented as the mean ± s.d. (n = 6 biological replicates). P values in a–e were calculated using an unpaired t-test.

Source data

Extended Data Fig. 3 Schematic illustration of epitope prediction and validation to examine the epitope basis of the effectiveness of iPM nanovax.

(a) Differentially shared membrane proteins identification. (b) Screening of immune epitopes for shared proteins. (c) The shared epitope-specific responses evoked by iPM nanovax. (d) Detecting the epitopes-specific responses in human PBMCs.

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Li, N., Qin, H., Zhu, F. et al. Potent prophylactic cancer vaccines harnessing surface antigens shared by tumour cells and induced pluripotent stem cells. Nat. Biomed. Eng 9, 215–233 (2025). https://doi.org/10.1038/s41551-024-01309-0

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