Ten tandem repeats of beta-hCG 109-118 enhance immunogenicity and anti-tumor effects of beta-hCG C-terminal peptide carried by mycobacterial heat-shock protein HSP65

Biochem Biophys Res Commun. 2006 Jul 14;345(4):1365-71. doi: 10.1016/j.bbrc.2006.05.022. Epub 2006 May 11.

Abstract

The beta-subunit of human chorionic gonadotropin (beta-hCG) is secreted by many kinds of tumors and it has been used as an ideal target antigen to develop vaccines against tumors. In view of the low immunogenicity of this self-peptide,we designed a method based on isocaudamer technique to repeat tandemly the 10-residue sequence X of beta-hCG (109-118), then 10 tandemly repeated copies of the 10-residue sequence combined with beta-hCG C-terminal 37 peptides were fused to mycobacterial heat-shock protein 65 to construct a fusion protein HSP65-X10-betahCGCTP37 as an immunogen. In this study, we examined the effect of the tandem repeats of this 10-residue sequence in eliciting an immune by comparing the immunogenicity and anti-tumor effects of the two immunogens, HSP65-X10-betahCGCTP37 and HSP65-betahCGCTP37 (without the 10 tandem repeats). Immunization of mice with the fusion protein HSP65-X10-betahCGCTP37 elicited much higher levels of specific anti-beta-hCG antibodies and more effectively inhibited the growth of Lewis lung carcinoma (LLC) in vivo than with HSP65-betahCGCTP37, which should suggest that HSP65-X10-betahCGCTP37 may be an effective protein vaccine for the treatment of beta-hCG-dependent tumors and multiple tandem repeats of a certain epitope are an efficient method to overcome the low immunogenicity of self-peptide antigens.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antibody Specificity / immunology
  • Bacterial Proteins / genetics
  • Bacterial Proteins / immunology*
  • Blotting, Western
  • Cancer Vaccines / genetics
  • Cancer Vaccines / immunology*
  • Cancer Vaccines / therapeutic use
  • Carcinoma, Lewis Lung / immunology
  • Carcinoma, Lewis Lung / pathology
  • Carcinoma, Lewis Lung / prevention & control
  • Cell Line, Tumor
  • Chaperonin 60
  • Chaperonins / genetics
  • Chaperonins / immunology*
  • Chorionic Gonadotropin, beta Subunit, Human / chemistry
  • Chorionic Gonadotropin, beta Subunit, Human / genetics*
  • Enzyme-Linked Immunosorbent Assay
  • Humans
  • Mice
  • Mice, Inbred C57BL
  • Peptide Fragments / genetics
  • Peptide Fragments / immunology*
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / immunology
  • Repetitive Sequences, Amino Acid / genetics*
  • Time Factors
  • Treatment Outcome
  • Vaccination / methods

Substances

  • Bacterial Proteins
  • Cancer Vaccines
  • Chaperonin 60
  • Chorionic Gonadotropin, beta Subunit, Human
  • Peptide Fragments
  • Recombinant Fusion Proteins
  • heat-shock protein 65, Mycobacterium
  • Chaperonins