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Fluorine-modified sialyl-Tn-CRM197 vaccine elicits a robust immune response

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Abstract

Even though a vaccine that targets tumor-associated carbohydrate antigens on epithelial carcinoma cells presents an attractive therapeutic approach, relatively poor immunogenicity limits its development. In this study, we investigated the immunological activity of a fluoro-substituted Sialyl-Tn (F-STn) analogue coupled to the non-toxic cross-reactive material of diphtheria toxin197 (CRM197). Our results indicate that F-STn-CRM197 promotes a greater immunogenicity than non-fluorinated STn-CRM197. In the presence or absence of adjuvant, F-STn-CRM197 remarkably enhances both cellular and humoral immunity against STn by increasing antigen-specific lymphocyte proliferation and inducing a mixed Th1/Th2 response leading to production of IFN-γ and IL-4 cytokines, as well as STn-specific antibodies. Furthermore, antisera produced from F-STn-CRM197 immunization significantly recognizes STn-positive tumor cells and increases cancer cell lysis induced by antibody-dependent cell-mediated cytotoxicity (ADCC) or complement-dependent cytotoxicity (CDC) pathways. Our data suggest that this F-STn vaccine may be useful for cancer immunotherapy and possibly for prophylactic prevention of cancer.

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Acknowledgements

We are grateful for the support by the grants (2017ZX09309025) from the Ministry of Science and Technology of China, the National Natural Science Foundation of China (21738001), the Scientific and Technologic Foundation of Jilin Province (20190103070JH), the Project funded by China Postdoctoral Science Foundation (2018 M640276), and the Fundamental Research Funds for the Central Universities (2412018QD012). We are grateful to Prof. Kevin H Mayo for critical reading and editing of this manuscript.

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  1. School of Life Sciences, Northeast Normal University, Changchun, 130024, China

    Chengcheng Song, Haili Guo, Fan Zhang & Yifa Zhou

  2. State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, 100191, China

    Chengcheng Song, Xiu-Jing Zheng, Yafei Cao, Qin Li & Xin-Shan Ye

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Xiu-Jing Zheng and Xin-Shan Ye have an ownership interest in the patent (China patent No. ZL 2010 10,202,388.5, Japan patent No. 5815687, Int. Appl. No. PCT/CN2011/000610). No potential conflicts of interest were disclosed by the other authors.

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Song, C., Zheng, XJ., Guo, H. et al. Fluorine-modified sialyl-Tn-CRM197 vaccine elicits a robust immune response. Glycoconj J 36, 399–408 (2019). https://doi.org/10.1007/s10719-019-09884-0

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