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.

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.

authors

Yankai Z,Rong Y,Yi H,Wentao L,Rongyue C,Ming Y,Taiming L,Jingjing L,Jie W

doi

10.1016/j.bbrc.2006.05.022

subject

Has Abstract

pub_date

2006-07-14 00:00:00

pages

1365-71

issue

4

eissn

0006-291X

issn

1090-2104

pii

S0006-291X(06)01045-X

journal_volume

345

pub_type

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