Antitumor Humoral and T Cell Responses by Mucin-1 Conjugates of Bacteriophage Qβ in Wild-type Mice

ACS Chem Biol. 2018 Jun 15;13(6):1668-1676. doi: 10.1021/acschembio.8b00313. Epub 2018 May 30.

Abstract

Mucin-1 (MUC1) is one of the top ranked tumor associated antigens. In order to generate effective anti-MUC1 immune responses as potential anticancer vaccines, MUC1 peptides and glycopeptides have been covalently conjugated to bacteriophage Qβ. Immunization of mice with these constructs led to highly potent antibody responses with IgG titers over one million, which are among the highest anti-MUC1 IgG titers reported to date. Furthermore, the high IgG antibody levels persisted for more than six months. The constructs also elicited MUC1 specific cytotoxic T cells, which can selectively kill MUC1 positive tumor cells. The unique abilities of Qβ-MUC1 conjugates to powerfully induce both antibody and cytotoxic T cell immunity targeting tumor cells bode well for future translation of the constructs as anticancer vaccines.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antibody Formation / immunology
  • Bacteriophages / chemistry
  • Bacteriophages / immunology*
  • Cancer Vaccines / chemical synthesis
  • Cancer Vaccines / immunology*
  • Cell Line, Tumor
  • Humans
  • Immunity, Humoral / immunology*
  • Immunization
  • Immunoglobulin G / immunology*
  • Lymphocyte Activation / immunology*
  • Lymphoma / immunology
  • Mice, Inbred C57BL
  • Microarray Analysis
  • Mucin-1 / chemistry
  • Mucin-1 / immunology*
  • T-Lymphocytes, Cytotoxic / immunology
  • Vaccines, Synthetic / chemistry
  • Vaccines, Synthetic / immunology

Substances

  • Cancer Vaccines
  • Immunoglobulin G
  • Mucin-1
  • Vaccines, Synthetic