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

• Published in: Cancer Immunology, Immunotherapy Vol. 59; no. 12; pp. 1859 - 1866
• Main Authors: Wang, Xue Jun, Gu, Kai, Xu, Jin Shu, Li, Ming Hui, Cao, Rong Yue, Wu, Jie, Li, Tai Ming, Liu, Jing Jing
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Berlin/Heidelberg : Springer-Verlag 01.12.2010; Springer-Verlag; Springer; Springer Nature B.V
• Subjects: Animals; Antibodies; Antineoplastic agents; Bacterial Proteins - immunology; Biological and medical sciences; Breast cancer; Cancer immunotherapy; Cancer Research; Cancer therapies; Cancer Vaccines - immunology; Chaperonin 60 - immunology; Female; GnRH; Gonadotropin-Releasing Hormone - immunology; Heat shock proteins; Hormone-dependent cancer; Hsp65; Immunization; Immunology; Immunotherapy; Laboratories; Mammary Neoplasms, Experimental - pathology; Mammary Neoplasms, Experimental - therapy; Measles; Medical sciences; Medicine; Medicine & Public Health; Mice; Mice, Inbred BALB C; Oncology; Original; Original Article; Ovaries; Peptides; Pharmacology. Drug treatments; Pharmacy; Prostate; Tumors; Vaccine; Vaccines; Vaccines, Synthetic - immunology; China; Hsp65; Vaccine; GnRH; Cancer immunotherapy; Hormone-dependent cancer; Hormonodependence; Immunization; Gonadotropin RH; Malignant tumor; Hypothalamic hormone; In vivo; Treatment; Tumor growth; Immunotherapy; Heat shock protein 65; Inhibitor; Mammary gland; Hormone releasing factor; Recombinant vaccine; Cancer
• ISSN: 0340-7004; 1432-0851
• DOI: 10.1007/s00262-010-0911-4

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-GnRH₆ containing heat shock protein 65 (Hsp65) and six copies of GnRH in linear alignment. Immunization with Hsp65-GnRH₆ 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-GnRH₆ 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-GnRH₆ appears to be a promising candidate vaccine for hormone-dependent cancer therapy.