Immunization with a recombinant GnRH vaccine fused to heat shock protein 65 inhibits mammary tumor growth in vivo.

Cancer Immunol Immunother

Key Laboratory of Human Functional Genomics of Jiangsu Province, Nanjing Medical University, Hanzhong Road 140, Nanjing, 210029, China.

Published: December 2010

AI Article Synopsis

  • GnRH is crucial for mammalian reproduction and its active immunization shows promise in treating hormone-dependent diseases like breast cancer.
  • The novel protein vaccine Hsp65-GnRH(6) successfully generated strong anti-GnRH antibodies in female mice, leading to ovary and uterus degeneration.
  • This immune response inhibited the growth of mammary tumors, suggesting that Hsp65-GnRH(6) could be an effective candidate for cancer therapy targeting hormone dependence.

Article Abstract

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.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11031030PMC
http://dx.doi.org/10.1007/s00262-010-0911-4DOI Listing

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