Identification of peptide mimotopes of gp96 using single-chain antibody library

Arulkumaran Shanmugam, Robert Suriano, Neha Goswami, Devyani Chaudhuri, Badithe T. Ashok, Shilpi Rajoria, Andrea L. George, Abraham Mittelman, Raj K. Tiwari

Research output: Contribution to journalArticle

4 Scopus citations

Abstract

Heat shock proteins such as gp96 are immunogenic and are widely used as vaccines in immunotherapy of cancers. The present study focuses on the use of peptide mimotopes as immunotherapeutic vaccines for prostate cancer. To this end, we developed a 15-mer gp96 peptide mimotope specifically reactive to MAT-LyLu gp96-peptide complex using combinatorial single-chain antibody and peptide phage display library. The immunogenicity of the synthesized gp96 mimotope was analyzed initially in normal BALB/c mice in combination with various adjuvants such as complete Freund's adjuvant (CFA), aluminum salts (ALUM), granulocyte-macrophage colony-stimulating factor (GM-CSF), and liposome, of which CFA served as a positive control. The antibody response was determined and found that the gp96 mimotope with ALUM showed a significant increase in antibody titer, followed by GM-CSF and liposomes. Further, the T cell (CD4 + and CD8+) populations from splenocytes, as well as IgG isotypes, interleukin-4, and interleukin-5 of gp96 mimotope with ALUM-immunized animals, were analyzed. The results suggest that the gp96 mimotope may elicit a potent and effective antitumor antibody response. Further, the study identifies ALUM and GM-CSF as adjuvant options to drive an appropriate protective immune response as these adjuvants have prior use in humans.

Original languageEnglish (US)
Pages (from-to)225-234
Number of pages10
JournalCell Stress and Chaperones
Volume16
Issue number2
DOIs
StatePublished - Mar 1 2011

Keywords

  • Heat shock protein
  • Mimotope
  • Phage display
  • Prostate cancer
  • gp96

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology

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    Shanmugam, A., Suriano, R., Goswami, N., Chaudhuri, D., Ashok, B. T., Rajoria, S., George, A. L., Mittelman, A., & Tiwari, R. K. (2011). Identification of peptide mimotopes of gp96 using single-chain antibody library. Cell Stress and Chaperones, 16(2), 225-234. https://doi.org/10.1007/s12192-010-0234-6