Immunization with a recombinant GnRH vaccine fused to heat shock protein 65 inhibits mammary tumor growth in vivo.
Gonadotrophin-releasing hormone (GnRH) is the prime decapeptide hormone in the regulation of mammalian reproduction. Active immunization against GnRH has been a good treatment option to fight against hormone-dependent disease such as breast cancer. We designed and purified a novel protein vaccine Hsp65-GnRH(6) containing heat shock protein 65 (Hsp65) and six copies of GnRH in linear alignment. Immunization with Hsp65-GnRH(6) evoked strong humoral response in female mice. The generation of specific anti-GnRH antibodies was detected by ELISA and verified by western blot. In addition, anti-GnRH antibodies effectively neutralized endogenous GnRH activity in vivo, as demonstrated by the degeneration of the ovaries and uteri in the vaccinated mice. Moreover, the growth of EMT-6 mammary tumor allografts was inhibited by anti-GnRH antibodies. Histological examinations have shown that there was increased focal necrosis in tumors. Taken together, our results showed that immunization with Hsp65-GnRH(6) elicited high titer of specific anti-GnRH antibodies and further led to atrophy of reproductive organs. The specific antibodies could inhibit the growth of EMT-6 murine mammary tumor probably via an indirect mechanism that includes the depletion of estrogen. In view of these results, the protein vaccine Hsp65-GnRH(6) appears to be a promising candidate vaccine for hormone-dependent cancer therapy.
Wang
Xue Jun
XJ
Key Laboratory of Human Functional Genomics of Jiangsu Province, Nanjing Medical University, Hanzhong Road 140, Nanjing, 210029, China. wangxuejun1979728@hotmail.com
Gu
Kai
K
Xu
Jin Shu
JS
Li
Ming Hui
MH
Cao
Rong Yue
RY
Wu
Jie
J
Li
Tai Ming
TM
Liu
Jing Jing
JJ
D000818:Animals; D001426:Bacterial Proteins / Q000276:immunology*; D019496:Cancer Vaccines / Q000276:immunology*; D018834:Chaperonin 60 / Q000276:immunology*; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000276:immunology*; D007114:Immunization; D008325:Mammary Neoplasms, Experimental / Q000473:pathology / Q000628:therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D014614:Vaccines, Synthetic / Q000276:immunology
D001426:Bacterial Proteins; D019496:Cancer Vaccines; D018834:Chaperonin 60; D014614:Vaccines, Synthetic; C074119:heat-shock protein 65, Mycobacterium; D007987:Gonadotropin-Releasing Hormone
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