Immunization with a recombinant GnRH vaccine conjugated to heat shock protein 65 inhibits tumor growth in orthotopic prostate cancer mouse model.
We have previously shown that anti-GnRH antibodies responses can be induced by synthetic GnRH3-hinge-MVP peptide. In this study, GnRH3-hinge-MVP of conjugation to heat shock protein 65 was used as an adjuvant-free vaccine to assess the therapeutic effects of GnRH immunoneutralisation on tumor development in the mice model. Compared with mice treated with Hsp65 and PBS, mice of the o.t. model receiving in situ treatment GnRH3-hinge-MVP-Hsp65 had significant prolongation of survival and suppression of local tumor growth. Serum levels of both testosterone and luteinizing hormone were reduced by treatment with GnRH3-hinge-MVP-Hsp65 (p<0.05). Further analyses of cell mediated immune responses showed that GnRH3-hinge-MVP-Hsp65 induced stronger lymphocyte proliferative responses and higher levels of IFN-gamma (p<0.001). The conjugation of the recombinant GnRH peptide to Hsp65 could be considered a promising approach for the development of an efficacious vaccine against the prostate cancer.
Xu
Jinshu
J
School of Pharmacy, Nanjing Medical University, Nanjing, PR China. jinshuuxu@yahoo.com
Zhu
Zheng
Z
Wu
Jie
J
Liu
Wentao
W
Shen
Xiangchun
X
Zhang
Yin
Y
Hu
Zhuoyi
Z
Zhu
Dongya
D
Roque
Rouel S
RS
Liu
Jingjing
J
D000818:Animals; D000917:Antibody Formation; D001426:Bacterial Proteins / Q000276:immunology*; D019496:Cancer Vaccines / Q000276:immunology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D018834:Chaperonin 60; D018833:Chaperonins / Q000276:immunology*; D007987:Gonadotropin-Releasing Hormone / Q000276:immunology*; D007111:Immunity, Cellular; D007074:Immunoglobulin G / Q000097:blood; D007371:Interferon-gamma / Q000378:metabolism; D007986:Luteinizing Hormone / Q000097:blood; D008213:Lymphocyte Activation; D008214:Lymphocytes / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009374:Neoplasms, Experimental / Q000276:immunology / Q000517:prevention & control; D011471:Prostatic Neoplasms / Q000097:blood / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D011994:Recombinant Proteins / Q000276:immunology; D013739:Testosterone / Q000097:blood; D013997:Time Factors; D018074:Vaccines, Conjugate / Q000276:immunology; D014614:Vaccines, Synthetic / Q000276:immunology; D014764:Viral Proteins / Q000276:immunology*
D001426:Bacterial Proteins; D019496:Cancer Vaccines; D018834:Chaperonin 60; C512006:GnRH3-hinge-MVP; D007074:Immunoglobulin G; D011994:Recombinant Proteins; D018074:Vaccines, Conjugate; D014614:Vaccines, Synthetic; D014764:Viral Proteins; C074119:heat-shock protein 65, Mycobacterium; D007987:Gonadotropin-Releasing Hormone; D013739:Testosterone; D007371:Interferon-gamma; D007986:Luteinizing Hormone; D018833:Chaperonins