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.
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.
Yankai
Zhang
Z
Minigene Pharmacy Laboratory, Biopharmaceutical College, China Pharmaceutical University, Tongjia Xiang 24, Nanjing, PR China.
Rong
Yan
Y
Yi
He
H
Wentao
Liu
L
Rongyue
Cao
C
Ming
Yan
Y
Taiming
Li
L
Jingjing
Liu
L
Jie
Wu
W
D000595:Amino Acid Sequence; D000818:Animals; D000918:Antibody Specificity / Q000276:immunology; D001426:Bacterial Proteins / Q000235:genetics / Q000276:immunology*; D015153:Blotting, Western; D019496:Cancer Vaccines / Q000235:genetics / Q000276:immunology* / Q000627:therapeutic use; D018827:Carcinoma, Lewis Lung / Q000276:immunology / Q000473:pathology / Q000517:prevention & control; D045744:Cell Line, Tumor; D018834:Chaperonin 60; D018833:Chaperonins / Q000235:genetics / Q000276:immunology*; D018997:Chorionic Gonadotropin, beta Subunit, Human / Q000737:chemistry / Q000235:genetics*; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D010446:Peptide Fragments / Q000235:genetics / Q000276:immunology*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology; D020449:Repetitive Sequences, Amino Acid / Q000235:genetics*; D013997:Time Factors; D016896:Treatment Outcome; D014611:Vaccination / Q000379:methods
D001426:Bacterial Proteins; D019496:Cancer Vaccines; D018834:Chaperonin 60; D018997:Chorionic Gonadotropin, beta Subunit, Human; D010446:Peptide Fragments; D011993:Recombinant Fusion Proteins; C074119:heat-shock protein 65, Mycobacterium; D018833:Chaperonins