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.
Keywords:
Cancer immunotherapy; Glycoconjugate vaccine; STn; TACAs.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Adjuvants, Immunologic / administration & dosage
-
Animals
-
Antibodies, Neoplasm / isolation & purification
-
Antibodies, Neoplasm / pharmacology*
-
Antibody-Dependent Cell Cytotoxicity / drug effects
-
Antigens, Tumor-Associated, Carbohydrate / chemistry*
-
Antigens, Tumor-Associated, Carbohydrate / immunology
-
Bacterial Proteins / chemistry
-
Bacterial Proteins / immunology
-
Bacterial Proteins / pharmacology*
-
Cancer Vaccines / chemical synthesis
-
Cancer Vaccines / immunology
-
Cancer Vaccines / pharmacology*
-
Cell Line, Tumor
-
Colonic Neoplasms / immunology
-
Colonic Neoplasms / pathology
-
Colonic Neoplasms / therapy*
-
Female
-
Gene Expression
-
Glycoconjugates / chemical synthesis
-
Glycoconjugates / immunology
-
Glycoconjugates / pharmacology*
-
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
Substances
-
Adjuvants, Immunologic
-
Antibodies, Neoplasm
-
Antigens, Tumor-Associated, Carbohydrate
-
Bacterial Proteins
-
Cancer Vaccines
-
Glycoconjugates
-
Il4 protein, mouse
-
Immune Sera
-
sialosyl-Tn antigen
-
CRM197 (non-toxic variant of diphtheria toxin)
-
Interleukin-4
-
Interferon-gamma