Abstract
Tumor-associated carbohydrate antigens (TACAs), which are aberrantly expressed on the surface of tumor cells, are important targets for anticancer vaccine development. Herein, several N-acyl modified Tn analogues were synthesized and conjugated with carrier protein CRM197. The immunological results of these glycoconjugates indicated that 6-CRM197 elicited higher titers of antibodies which cross-reacted with native Tn antigen than the unmodified 2-CRM197 did. The IFN-γ-producing frequency of lymphocytes in mice treated with 6-CRM197 was obviously increased, compared to that of mice vaccinated with 2-CRM197 (p=0.016), which was typically associated with the Th1 response. Moreover, the elicited antisera against antigen 6-CRM197 reacted strongly with the Tn-positive tumor cells, implying the potential of this glycoconjugate as an anticancer vaccine.
Keywords:
Anticancer; Carbohydrate; Glycoconjugate; Tn antigen; Vaccine.
Copyright © 2016 Elsevier Ltd. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Acylation
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Animals
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Antibodies, Neoplasm / biosynthesis*
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Antigens, Tumor-Associated, Carbohydrate / chemistry
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Antigens, Tumor-Associated, Carbohydrate / immunology*
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Bacterial Proteins / administration & dosage
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Bacterial Proteins / chemistry
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Bacterial Proteins / immunology*
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Cancer Vaccines / administration & dosage
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Cancer Vaccines / chemistry
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Cancer Vaccines / immunology*
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Diphtheria Toxin / administration & dosage
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Diphtheria Toxin / chemistry
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Diphtheria Toxin / immunology
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Female
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Glycoconjugates / administration & dosage
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Glycoconjugates / chemical synthesis
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Glycoconjugates / immunology*
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Humans
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Immune Sera / chemistry
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Immunity, Humoral / drug effects
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Immunoglobulin G / biosynthesis
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Interferon-gamma / biosynthesis*
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Jurkat Cells
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MCF-7 Cells
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Mice
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Mice, Inbred BALB C
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Th1 Cells / drug effects
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Th1 Cells / immunology
Substances
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Antibodies, Neoplasm
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Antigens, Tumor-Associated, Carbohydrate
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Bacterial Proteins
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Cancer Vaccines
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Diphtheria Toxin
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Glycoconjugates
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Immune Sera
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Immunoglobulin G
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Tn antigen
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CRM197 (non-toxic variant of diphtheria toxin)
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Interferon-gamma