Induction of antibody responses to breast carcinoma associated mucins using synthetic peptide constructs as immunogens

Cancer Lett. 1993 Jul 16;70(3):143-50. doi: 10.1016/0304-3835(93)90224-w.

Abstract

A strategy for directing and enhancing B cell immune responses against synthetic peptide determinants has been developed in order to produce antibodies specifically against protein epitopes of clinical relevance. A peptide sequence based upon the MUC-1 mucin protein core was selected for this purpose since anti-MUC-1 antibodies have proven diagnostic application and therapeutic potential in human breast and ovarian cancer. Peptide constructs were synthesised co-linearly linking the immunodominant B cell determinant region, PDTRPAP, in the protein core of the MUC-1 mucin, to sequence 111-120 of influenza haemagglutinin A/X-31, a determinant recognised by T helper cells through association with MHC class II molecules. Induction of anti-MUC-1 antibodies to the B cell determinant region by immunisation with peptide was shown to be dependent upon both the presence and the position of the T cell determinant. In addition, haplotype mismatching with respect to the T cell determinant resulted in a significant lowering of the anti-MUC-1 antibody response in peptide construct immunised mice. These findings are relevant to the design of immunogens to produce antibodies against peptide epitopes of tumour associated proteins and glycoproteins.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antibodies, Neoplasm / biosynthesis*
  • Antibodies, Neoplasm / immunology
  • Antigens, Neoplasm / chemistry
  • Antigens, Neoplasm / immunology*
  • B-Lymphocytes / immunology
  • Breast Neoplasms / immunology*
  • Enzyme-Linked Immunosorbent Assay
  • Epitopes / chemistry
  • Epitopes / immunology
  • Female
  • Haplotypes
  • Hemagglutinin Glycoproteins, Influenza Virus
  • Hemagglutinins, Viral / immunology
  • Immune Sera / immunology
  • Immunization
  • Immunotherapy
  • Membrane Glycoproteins / chemistry
  • Membrane Glycoproteins / immunology*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Inbred CBA
  • Molecular Sequence Data
  • Mucin-1
  • Mucins / chemistry
  • Mucins / immunology*
  • Neoplasm Proteins / chemistry
  • Neoplasm Proteins / immunology*
  • Peptide Fragments / immunology*
  • Peptide Mapping
  • T-Lymphocytes / immunology
  • Viral Envelope Proteins / immunology

Substances

  • Antibodies, Neoplasm
  • Antigens, Neoplasm
  • Epitopes
  • Hemagglutinin Glycoproteins, Influenza Virus
  • Hemagglutinins, Viral
  • Immune Sera
  • Membrane Glycoproteins
  • Mucin-1
  • Mucins
  • Neoplasm Proteins
  • Peptide Fragments
  • Viral Envelope Proteins