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

Autor: Xin-Shan Ye, Yifa Zhou, Haili Guo, Fan Zhang, Qin Li, Chengcheng Song, Xiu-Jing Zheng, Yafei Cao
Rok vydání: 2019
Předmět:
Halogenation
Antibodies
Neoplasm
medicine.medical_treatment
Gene Expression
Lymphocyte proliferation
Biochemistry
Mice
Immunogenicity
Vaccine
Cancer immunotherapy
Lymphocytes
Th1-Th2 Balance
Antibody-dependent cell-mediated cytotoxicity
0303 health sciences
Immunity
Cellular
Mice
Inbred BALB C
Chemistry
Immunogenicity
030302 biochemistry & molecular biology
surgical procedures
operative
Colonic Neoplasms
Female
therapeutics
Adjuvant
Cancer Vaccines
03 medical and health sciences
Interferon-gamma
Immune system
Antigen
Adjuvants
Immunologic
Bacterial Proteins
Cell Line
Tumor
medicine
Animals
Humans
Antigens
Tumor-Associated
Carbohydrate
Molecular Biology
030304 developmental biology
Immune Sera
Antibody-Dependent Cell Cytotoxicity
Cell Biology
nervous system diseases
Immunity
Humoral
nervous system
Humoral immunity
Cancer research
Immunization
sense organs
Interleukin-4
Glycoconjugates
Spleen
Zdroj: Glycoconjugate journal. 36(5)
ISSN: 1573-4986
Popis: 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.
Databáze: OpenAIRE
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