Multiantigenic peptide–polymer conjugates as therapeutic vaccines against cervical cancer

Waleed M. Hussein, Tzu Yu Liu, Zhongfan Jia, Nigel A.J. McMillan, Michael J. Monteiro, Istvan Toth, Mariusz Skwarczynski

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Immunotherapy is one of the most promising strategies for the treatment of cancer. Human papillomavirus (HPV) is responsible for virtually all cases of cervical cancer. The main purpose of a therapeutic HPV vaccine is to stimulate CD8+cytotoxic T lymphocytes (CTLs) that can eradicate HPV infected cells. HPV oncoproteins E6 and E7 are continuously expressed and are essential for maintaining the growth of HPV-associated tumor cells. We designed polymer-based multi-antigenic formulations/constructs that were comprised of the E6 and E7 peptide epitopes. We developed an N-terminus-based epitope conjugation to conjugate two unprotected peptides to poly tert-butyl acrylate. This method allowed for the incorporation of the two antigens into a polymeric dendrimer in a strictly equimolar ratio. The most effective formulations eliminated tumors in up to 50% of treated mice. Tumor recurrence was not observed up to 3 months post initial challenge.

Original languageEnglish
Pages (from-to)4372-4380
Number of pages9
JournalBioorganic & Medicinal Chemistry
Volume24
Issue number18
DOIs
Publication statusPublished - 15 Sep 2016
Externally publishedYes

Keywords

  • Cervical cancer
  • Human papillomavirus
  • Multiantigenic
  • Peptide-based subunit vaccine
  • Polymer–peptide conjugate
  • Self-adjuvanting
  • Therapeutic cancer vaccine

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  • Cite this

    Hussein, W. M., Liu, T. Y., Jia, Z., McMillan, N. A. J., Monteiro, M. J., Toth, I., & Skwarczynski, M. (2016). Multiantigenic peptide–polymer conjugates as therapeutic vaccines against cervical cancer. Bioorganic & Medicinal Chemistry, 24(18), 4372-4380. https://doi.org/10.1016/j.bmc.2016.07.036