Synthesis and immunological evaluation of N-acyl modified Tn analogues as anticancer vaccine candidates

Bioorg Med Chem. 2016 Feb 15;24(4):915-20. doi: 10.1016/j.bmc.2016.01.015. Epub 2016 Jan 8.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acylation
  • Animals
  • Antibodies, Neoplasm / biosynthesis*
  • Antigens, Tumor-Associated, Carbohydrate / chemistry
  • Antigens, Tumor-Associated, Carbohydrate / immunology*
  • Bacterial Proteins / administration & dosage
  • Bacterial Proteins / chemistry
  • Bacterial Proteins / immunology*
  • Cancer Vaccines / administration & dosage
  • Cancer Vaccines / chemistry
  • Cancer Vaccines / immunology*
  • Diphtheria Toxin / administration & dosage
  • Diphtheria Toxin / chemistry
  • Diphtheria Toxin / immunology
  • Female
  • Glycoconjugates / administration & dosage
  • Glycoconjugates / chemical synthesis
  • Glycoconjugates / immunology*
  • Humans
  • Immune Sera / chemistry
  • Immunity, Humoral / drug effects
  • Immunoglobulin G / biosynthesis
  • Interferon-gamma / biosynthesis*
  • Jurkat Cells
  • MCF-7 Cells
  • Mice
  • Mice, Inbred BALB C
  • Th1 Cells / drug effects
  • Th1 Cells / immunology

Substances

  • Antibodies, Neoplasm
  • Antigens, Tumor-Associated, Carbohydrate
  • Bacterial Proteins
  • Cancer Vaccines
  • Diphtheria Toxin
  • Glycoconjugates
  • Immune Sera
  • Immunoglobulin G
  • Tn antigen
  • CRM197 (non-toxic variant of diphtheria toxin)
  • Interferon-gamma