The fusion protein of HSP65 with tandem repeats of beta-hCG acting as a potent tumor vaccine in suppressing hepatocarcinoma.
It has been demonstrated that the beta-subunit of human chorionic gonadotropin (beta-hCG) is ectopically expressed on a variety of human cancers of different histological types and has been used as an antigenic target in anti-cancer vaccines. We engineered a fusion protein by fusing 10 tandemly repeated copies of the 10-residue sequence of beta-hCG (109-118) (in CTP37) combined with beta-hCG C-terminal 37 peptides to mycobacterial heat-shock protein 65 and immunized mice via subcutaneous injection. Humoral immune and cellular immune responses were effectively elicited. High titer of anti-beta-hCG antibody was detected in immunized mice sera by ELISA and verified by Western blot analyses. The fusion protein of HSP65-X10-beta-hCGCTP37 effectively inhibited the growth of tumor both protective and therapeutic anti-tumor immunity in hepatocellular carcinoma tumor models in mice. Meanwhile, it also attenuated tumor-induced angiogenesis in intradermal tumor model in mice. Taken together, these results demonstrate that immune responses are effectively induced by a novel fusion protein vaccine targeting beta-hCG, suppressing the growth of hepatocellular carcinoma in mice. The beta-hCG-targeted vaccine holds promise for the treatment of a number of cancers and merits further study.
Xiangbing
Hu
H
Minigene Pharmacy Laboratory, Biopharmaceutical College, China Pharmaceutical University, Tongjia Xiang 24, Nanjing, 210009, PR China.
Yankai
Zhang
Z
Ming
Lin
L
Yong
Lu
L
Yu
Zhang
Z
Huiyong
Zhang
Z
Yingying
Chen
C
Jing
Hou
H
Yun
Xing
X
Liang
Jin
J
Rongyue
Cao
C
Jingjing
Liu
L
D000818:Animals; D000912:Antibodies, Neoplasm / Q000276:immunology; D000918:Antibody Specificity / Q000276:immunology; D001426:Bacterial Proteins / Q000235:genetics / Q000276:immunology* / Q000627:therapeutic use; D019496:Cancer Vaccines / Q000235:genetics / Q000276:immunology* / Q000627:therapeutic use; D006528:Carcinoma, Hepatocellular / Q000276:immunology / Q000628:therapy*; D018834:Chaperonin 60 / Q000235:genetics / Q000276:immunology* / Q000627:therapeutic use; D018997:Chorionic Gonadotropin, beta Subunit, Human / Q000235:genetics / Q000276:immunology* / Q000627:therapeutic use; D008113:Liver Neoplasms / Q000276:immunology / Q000628:therapy*; D008297:Male; D051379:Mice; D009389:Neovascularization, Pathologic / Q000276:immunology; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology* / Q000627:therapeutic use; D020080:Tandem Repeat Sequences
D000912:Antibodies, Neoplasm; D001426:Bacterial Proteins; D019496:Cancer Vaccines; D018834:Chaperonin 60; D018997:Chorionic Gonadotropin, beta Subunit, Human; D011993:Recombinant Fusion Proteins; C074119:heat-shock protein 65, Mycobacterium