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Synthesis and Evaluation of Glycoconjugates Comprising N-Acyl-Modified Thomsen-Friedenreich Antigens as Anticancer Vaccines
- Source :
- ChemMedChem. 11(10)
- Publication Year :
- 2016
-
Abstract
- Thomsen-Friedenreich (TF) antigen is an important tumor-associated carbohydrate antigen. Its low immunogenicity, however, limits its application in the development of anticancer vaccines. To solve this problem, several N-acyl-modified TF derivatives were synthesized and conjugated with carrier protein CRM197 (a mutated diphtheria toxoid cross-reactive material). The immunological results in BALB/c mice demonstrated that these modified TF antigen conjugates could stimulate the production of higher titers of IgG antibodies that cross-reacted with native TF antigen. These glycoconjugates showed strong lymphocyte proliferative response, suggesting that they can induce cellular immunity. Furthermore, the elicited antisera reacted strongly with TF-positive tumor cells (4T1). In particular, the N-monofluoroacetyl-modified TF conjugate 4-CRM197 showed the strongest complement-dependent cytotoxicity effect against 4T1 cells, implying the potential of this glycoconjugate as an anticancer vaccine.
- Subjects :
- Cellular immunity
Glycoconjugate
Cell Survival
Lymphocyte
Biology
010402 general chemistry
01 natural sciences
Biochemistry
Cancer Vaccines
Cell Line
Mice
Antigen
Bacterial Proteins
Drug Discovery
medicine
Animals
Antigens, Tumor-Associated, Carbohydrate
Lymphocytes
General Pharmacology, Toxicology and Pharmaceutics
Pharmacology
chemistry.chemical_classification
Antiserum
Diphtheria toxin
Mice, Inbred BALB C
010405 organic chemistry
Immunogenicity
Organic Chemistry
Molecular biology
0104 chemical sciences
medicine.anatomical_structure
chemistry
Immunoglobulin G
biology.protein
Molecular Medicine
Female
Antibody
Glycoconjugates
Subjects
Details
- ISSN :
- 18607187
- Volume :
- 11
- Issue :
- 10
- Database :
- OpenAIRE
- Journal :
- ChemMedChem
- Accession number :
- edsair.doi.dedup.....18c28f15549b7a3d1416743f82b1b14a