Inhibition effects on liver tumors of BALB/c mice bearing H22 cells by immunization with a recombinant immunogen of GnRH linked to heat shock protein 65.
In the following study, we prepared a double-chain miniprotein with each chain containing three linear repeats of the self-peptide gonadotropin-releasing hormone (GnRH(3)), the hinge region of human IgG1 (hinge), and a T-helper epitope from the measles virus protein (MVP). The di-GnRH(3)-hinge-MVP miniprotein was conjugated to purified recombinant heat shock protein 65 (Hsp65) of Mycobacterium bovis and used to immunize BALB/c mice primed with subcutaneous injection of Bacillus Calmette-Gurerin (BCG) in the absence of adjuvants. After anti-GnRH antibodies were successfully produced, mice were inoculated with H22 cells as a solid tumor. The results showed that after GnRH was inhibited by anti-GnRH antibodies the testosterone levels in sera markedly decreased (P<0.01) and the testicle weights reduced as well (P<0.05) in GnRH(3)-hinge-MVP-Hsp65-immunized mice. The average weight of tumors in mice treated with GnRH(3)-hinge-MVP-Hsp65 was significantly lower than in mice treated with saline only (neutral control, P<0.001), or less than in mice treated with Hsp65 (negative control, P<0.005). The data reported here demonstrated that GnRH(3)-hinge-MVP-Hsp65 could significantly attenuate the progression of liver tumor in mice transplanted with H22 cells, and might develop to be palliative treatment of hepatocellular carcinoma (HCC) patients in the future.
Zhang
Yin
Y
Life Sciences College, Nanjing Normal University, Wenyuan Road 1, Nanjing 210046, Jiangsu, People's Republic of China.
Xu
Jinshu
J
Zhao
Renping
R
Liu
Jingjing
J
Wu
Jie
J
D000595:Amino Acid Sequence; D000818:Animals; D000912:Antibodies, Neoplasm / Q000097:blood; D001426:Bacterial Proteins / Q000235:genetics / Q000276:immunology*; D006528:Carcinoma, Hepatocellular / Q000517:prevention & control*; D045744:Cell Line, Tumor; D018834:Chaperonin 60; D018833:Chaperonins / Q000235:genetics / Q000276:immunology*; D007987:Gonadotropin-Releasing Hormone / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007114:Immunization; D007167:Immunotherapy; D008113:Liver Neoplasms / Q000517:prevention & control*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D013739:Testosterone / Q000032:analysis; D022223:Vaccines, Subunit / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D014764:Viral Proteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology*
D000912:Antibodies, Neoplasm; D001426:Bacterial Proteins; D018834:Chaperonin 60; C512005:GnRH-hinge-MVP peptide; D022223:Vaccines, Subunit; D014614:Vaccines, Synthetic; D014764:Viral Proteins; C074119:heat-shock protein 65, Mycobacterium; D007987:Gonadotropin-Releasing Hormone; D013739:Testosterone; D018833:Chaperonins