Vaccination against gonadotropin-releasing hormone (GnRH) using toxin receptor-binding domain-conjugated GnRH repeats

Chia Tse Hsu, Chun Yuan Ting, Chun Jen Ting, Tzong Yueh Chen, Chia Po Lin, Jacqueline Whang-Peng, J. Hwang

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Abstract

A method for the preparation of an immunogen containing multiple copies of a self-peptide in linear alignment was designed in order to overcome the difficulty of inducing an immune response to poorly immunogenic peptide antigens. DNA fragments encoding multiple repeats of the self-peptide were generated by a new technique, termed template-repeated polymerase chain reaction (TR-PCR), which could be subcloned into an expression vector for production of peptide repeats as an immunogen. This approach was tested by constructing fusion proteins containing the receptor-binding domain of Pseudomonas exotoxin A and multiple copies of the 10-residue sequence of the peptide hormone gonadotropin-releasing hormone (GnRH). Immunization of female rabbits with the immunogen that contained the exotoxin receptor-binding domain and 12 copies of GnRH (PEIa-GnRH12) resulted in the generation of high-titer antibodies specific for GnRH. Although at equal molar basis of the GnRH moiety, the immunogen that contained single copy of GnRH (PEIa-GnRH1) induced low-titer anti-GnRH antibodies. These observations suggest that the presence of multiple peptide repeats is a key factor in eliciting an immune response. In addition, anti-GnRH antibodies effectively neutralized GnRH activity in vivo, as demonstrated by the degeneration of the ovaries in the injected rabbits. Because anti-GnRH antibody could be functionally analogous to GnRH antagonist, which has been used to treat patients with ovarian cancer, vaccination of PEIa-GnRH12 presents a potential therapeutic application for the treatment of GnRH-sensitive ovarian cancer.

Original languageEnglish
Pages (from-to)3701-3705
Number of pages5
JournalCancer Research
Volume60
Issue number14
Publication statusPublished - Jul 15 2000
Externally publishedYes

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ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Hsu, C. T., Ting, C. Y., Ting, C. J., Chen, T. Y., Lin, C. P., Whang-Peng, J., & Hwang, J. (2000). Vaccination against gonadotropin-releasing hormone (GnRH) using toxin receptor-binding domain-conjugated GnRH repeats. Cancer Research, 60(14), 3701-3705.