title: Evaluation of the immunogenicity of a single chain chimeric peptide composed of hCGβ and oLHα for inhibition of the growth of hCGβ-expressing cancer cells.
abstract: Human chorionic gonadotropin (hCG) is a membrane-associated protein highly expressed in several types of human cancer cells. The expression in the cancer cells indicates that hCG may be a potential target molecule for cancer immunotherapy. The objective of this study was to develop a novel immunogenic molecule, which can efficiently induce the neutralizing antibody against hCG and which is also suitable for mass production. The immunogenicity of the recombinant single chain chimeric protein of hCGβ-oLHα expressed by yeast was examined. Additionally, the inhibitory effects of the anti-hCGβ-oLHα antibody on the growth of hCG-positive cancer cells were determined. It was found that hCGβ-oLHα yielded high titers of anti-hCG rabbit antibody that could effectively neutralize the bioactivity of hCG. The rabbit anti-hCGβ-oLHα IgG inhibited the proliferation of hCG-expressing human colorectal cancer cells (LS-174, HCT-116, HCT-15 and KM-12) in a dose-dependent manner. Furthermore, an intact anti-tumor vaccine was prepared by conjugating hCGβ-oLHα with tetanus toxoid (TT) and this was used to immunize Balb/c mice bearing hCG-expressing SP2/0 tumor cells. The progression of tumors in these immunized mice was remarkably inhibited. These results suggest that hCGβ-oLHα is a new promising immunogenic molecule for the development of an anti-hCG-based cancer vaccine.
authors.affiliation: NPFPC Key Laboratory of Contraceptives and Devices, Shanghai Institute of Planned Parenthood Research, Shanghai, 200032, China.
authors.forename: Chu
authors.initials: C
authors.lastname: Jiang
authors.forename: Yahong
authors.initials: Y
authors.lastname: Jiang
authors.forename: Zheping
authors.initials: Z
authors.lastname: Huang
authors.forename: Weiying
authors.initials: W
authors.lastname: Shen
authors.forename: Jian
authors.initials: J
authors.lastname: Wang
authors.forename: Qingxiang
authors.initials: Q
authors.lastname: Shen
mesh_terms: D000818:Animals; D019496:Cancer Vaccines / Q000276:immunology*; D045744:Cell Line, Tumor; D018997:Chorionic Gonadotropin, beta Subunit, Human / Q000032:analysis / Q000276:immunology*; D015292:Glycoprotein Hormones, alpha Subunit / Q000276:immunology*; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009374:Neoplasms, Experimental / Q000473:pathology / Q000628:therapy*; D011817:Rabbits; D011993:Recombinant Fusion Proteins / Q000276:immunology*; D013745:Tetanus Toxoid / Q000008:administration & dosage; D014611:Vaccination
chemical_list: D019496:Cancer Vaccines; D018997:Chorionic Gonadotropin, beta Subunit, Human; D015292:Glycoprotein Hormones, alpha Subunit; D011993:Recombinant Fusion Proteins; D013745:Tetanus Toxoid
references.citation: Cancer. 1992 Apr 1;69(7):1818-28
references.pmid: 1372527
references.citation: Oncol Rep. 1999 Jan-Feb;6(1):7-17
references.pmid: 9864394
references.citation: Cutis. 2001 Feb;67(2):117-20
references.pmid: 11236220
references.citation: Mol Cell Endocrinol. 1996 Dec 20;125(1-2):71-7
references.pmid: 9027345
references.citation: Mol Cell Endocrinol. 2007 Jan 2;260-262:276-81
references.pmid: 17049720
references.citation: Cancer. 1995 Oct 15;76(8):1467-75
references.pmid: 8620425
references.citation: Int Rev Immunol. 2003 Mar-Apr;22(2):81-112
references.pmid: 12962271
references.citation: Nucleic Acids Res. 1989 Dec 25;17(24):10494
references.pmid: 2481272
references.citation: Nature. 1980 Aug 14;286(5774):684-7
references.pmid: 6774259
references.citation: Hum Reprod. 2005 Dec;20(12):3271-83
references.pmid: 16113040
references.citation: Ann Urol (Paris). 2001 Mar;35(2):125-8
references.pmid: 11355283
references.citation: Hum Reprod Update. 1997 Jul-Aug;3(4):301-10
references.pmid: 9459276
references.citation: J Allergy Clin Immunol. 2010 Feb;125(2 Suppl 2):S272-83
references.pmid: 20061007
references.citation: Int J Cancer. 2001 Jan 20;95(1):18-22
references.pmid: 11241305
references.citation: Clin Biochem. 2004 Jul;37(7):549-61
references.pmid: 15234236
references.citation: Int J Gynecol Cancer. 2001 May-Jun;11(3):251-4
references.pmid: 11437936
references.citation: Clin Cancer Res. 2004 Mar 15;10(6):1920-7
references.pmid: 15041707
references.citation: Lab Invest. 1997 Jun;76(6):859-71
references.pmid: 9194861
references.citation: Mol Cell Endocrinol. 2010 Nov 25;329(1-2):62-70
references.pmid: 20654692
references.citation: Fertil Steril. 2001 Aug;76(2):332-6
references.pmid: 11476781
references.citation: Cancer Res. 1995 Sep 1;55(17):3735-8
references.pmid: 7543817
references.citation: Tumour Biol. 2004 Jan-Apr;25(1-2):18-23
references.pmid: 15192308
references.citation: Br J Cancer. 2002 Jan 21;86(2):185-9
references.pmid: 11870503
references.citation: Immunol Rev. 1999 Oct;171:173-92
references.pmid: 10582171
references.citation: J Reprod Immunol. 1988 Dec;14(3):203-12
references.pmid: 3147333
references.citation: Prostate. 2002 Nov 1;53(3):200-10
references.pmid: 12386920
references.citation: Proc Natl Acad Sci U S A. 1979 Dec;76(12):6622-6
references.pmid: 230516
references.citation: Shi Yan Sheng Wu Xue Bao. 1998 Mar;31(1):61-8
references.pmid: 12014113
references.citation: Clin Cancer Res. 2002 Jul;8(7):2044-51
references.pmid: 12114402
references.citation: J Clin Endocrinol Metab. 1955 Apr;15(4):424-34
references.pmid: 14367457
references.citation: Am J Reprod Immunol. 1997 Feb;37(2):153-60
references.pmid: 9083611
references.citation: Am J Reprod Immunol. 1998 Jun;39(6):395-8
references.pmid: 9645272
references.citation: Proc Natl Acad Sci U S A. 1994 Aug 30;91(18):8532-6
references.pmid: 8078917