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Fluorine-modified sialyl-Tn-CRM197 vaccine elicits a robust immune response.
- Source :
-
Glycoconjugate journal [Glycoconj J] 2019 Oct; Vol. 36 (5), pp. 399-408. Date of Electronic Publication: 2019 Jul 02. - Publication Year :
- 2019
-
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.
- Subjects :
- Adjuvants, Immunologic administration & dosage
Animals
Antibodies, Neoplasm isolation & purification
Antibody-Dependent Cell Cytotoxicity drug effects
Antigens, Tumor-Associated, Carbohydrate immunology
Bacterial Proteins chemistry
Bacterial Proteins immunology
Cancer Vaccines chemical synthesis
Cancer Vaccines immunology
Cell Line, Tumor
Colonic Neoplasms immunology
Colonic Neoplasms pathology
Female
Gene Expression
Glycoconjugates chemical synthesis
Glycoconjugates immunology
Halogenation
Humans
Immune Sera chemistry
Immune Sera pharmacology
Immunity, Cellular drug effects
Immunity, Humoral drug effects
Immunization
Immunogenicity, Vaccine
Interferon-gamma genetics
Interferon-gamma immunology
Interleukin-4 genetics
Interleukin-4 immunology
Lymphocytes drug effects
Lymphocytes immunology
Mice
Mice, Inbred BALB C
Spleen drug effects
Spleen immunology
Th1-Th2 Balance
Antibodies, Neoplasm pharmacology
Antigens, Tumor-Associated, Carbohydrate chemistry
Bacterial Proteins pharmacology
Cancer Vaccines pharmacology
Colonic Neoplasms therapy
Glycoconjugates pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1573-4986
- Volume :
- 36
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Glycoconjugate journal
- Publication Type :
- Academic Journal
- Accession number :
- 31267246
- Full Text :
- https://doi.org/10.1007/s10719-019-09884-0