title: Vaccination with the repeat β-hCG C-terminal peptide carried by heat shock protein-65 (HSP65) for inducing antitumor effects.
abstract: The β-subunit of human chorionic gonadotropin (β-hCG) is ectopically expressed in various types of cancer and has been utilized as an antigenic target in anti-cancer vaccines. In view of the low immunogenicity of this self-peptide, we designed a method based on the isocaudamer technique to generate 14 tandem repeats of the 10-residue sequence X of β-hCG (109-118). These tandemly repeated copies were then combined with β-hCG C-terminal 37 peptides (CTP37) and finally fused to mycobacterial heat-shock protein 65 (HSP65) to construct a fusion protein HSP65-X14-βhCGCTP37 as an immunogen. In this study, BALB/c female mice were immunized via subcutaneous injection of the designed protein. Humoral immune and cellular immune responses were effectively elicited. A high titer of anti-β-hCG antibody was detected in immunized mice sera by enzyme-linked immunosorbent assay and verified by Western blot analysis. The fusion protein, HSP65-X14-β-hCGCTP37, effectively inhibited the growth of Ehrlich ascites carcinoma in mice. These results suggest that HSP65-X14-βhCGCTP37 may be an effective tumor vaccine, and the use of multiple tandem repeats of a certain epitope is an effective method to overcome the low immunogenicity of self-peptide antigens.
authors: Minigene Pharmacy Laboratory, School of Life Science and Technology, China Pharmaceutical University, 24 Tongjia Xiang, Nanjing, 210009, People's Republic of China.
authors: Jie
authors: J
authors: Yang
authors: Yankai
authors: Y
authors: Zhang
authors: Huaqian
authors: H
authors: Wang
authors: Zhenqiu
authors: Z
authors: Gao
authors: Zeyu
authors: Z
authors: Wang
authors: Bin
authors: B
authors: Liu
authors: Xiuhua
authors: X
authors: Zhang
authors: Mingzhu
authors: M
authors: Du
authors: Xiao
authors: X
authors: Huang
authors: Maolei
authors: M
authors: Xu
authors: Jie
authors: J
authors: Wu
authors: Taiming
authors: T
authors: Li
authors: Jingjing
authors: J
authors: Liu
authors: Rongyue
authors: R
authors: Cao
mesh_terms: D000818:Animals; D000906:Antibodies / Q000097:blood / Q000276:immunology; D001426:Bacterial Proteins / Q000235:genetics*; D001483:Base Sequence; D019496:Cancer Vaccines / Q000235:genetics / Q000276:immunology*; D045744:Cell Line, Tumor; D018834:Chaperonin 60 / Q000235:genetics*; D018997:Chorionic Gonadotropin, beta Subunit, Human / Q000235:genetics / Q000276:immunology*; D005260:Female; D023061:Gene Order; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology; D008214:Lymphocytes / Q000276:immunology; D051379:Mice; D009369:Neoplasms / Q000235:genetics / Q000276:immunology / Q000628:therapy; D010455:Peptides / Q000276:immunology*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology*; D014611:Vaccination
chemical_list: D000906:Antibodies; D001426:Bacterial Proteins; D019496:Cancer Vaccines; D018834:Chaperonin 60; D018997:Chorionic Gonadotropin, beta Subunit, Human; C576998:HSP65-X14-betahCGCTP37 fusion protein; D010455:Peptides; D011993:Recombinant Fusion Proteins; C074119:heat-shock protein 65, Mycobacterium