Journal
GLYCOCONJUGATE JOURNAL
Volume 36, Issue 5, Pages 399-408Publisher
SPRINGER
DOI: 10.1007/s10719-019-09884-0
Keywords
TACAs; STn; Glycoconjugate vaccine; Cancer immunotherapy
Categories
Funding
- Ministry of Science and Technology of China [2017ZX09309025]
- National Natural Science Foundation of China [21738001]
- Scientific and Technologic Foundation of Jilin Province
- China Postdoctoral Science Foundation [20190103070JH]
- Fundamental Research Funds for the Central Universities [2018 M640276]
- [2412018QD012]
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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-gamma 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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