Polyacrylate-based delivery system for self-adjuvanting anticancer peptide vaccine

Tzu Yu Liu, Waleed M. Hussein, Ashwini Kumar Giddam, Zhongfan Jia, Jennifer M. Reiman, Mehfuz Zaman, Nigel A.J. McMillan, Michael F. Good, Michael J. Monteiro, Istvan Toth, Mariusz Skwarczynski

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28 Citations (Scopus)

Abstract

Vaccination can provide a safe alternative to chemotherapy by using the body's natural defense mechanisms to create a potent immune response against tumor cells. Peptide-based therapeutic vaccines against human papillomavirus (HPV)-related cancers are usually designed to elicit cytotoxic T cell responses by targeting the HPV-16 E7 oncoprotein. However, peptides alone lack immunogenicity, and an additional adjuvant or external delivery system is required. In this study, we developed new polymer-peptide conjugates to create an efficient self-adjuvanting system for peptide-based therapeutic vaccines. These conjugates reduced tumor growth and eradicated E7-positive TC-1 tumors in mice after a "ingle shot" immunization, without the help from an external adjuvant. The new conjugates had a significantly higher anticancer efficacy than the antigen formulated with a commercial adjuvant. Furthermore, the polymer-peptide conjugates were promptly taken up by antigen presenting cells, including dendritic cells and macrophages, and efficiently activated CD4+ T-helper cells and CD8+ cytotoxic T lymphocyte cells.

Original languageEnglish
Pages (from-to)888-896
Number of pages9
JournalJournal of Medicinal Chemistry
Volume58
Issue number2
DOIs
Publication statusPublished - 9 Dec 2014
Externally publishedYes

Keywords

  • Polyacrylate-based
  • Anticancer
  • Peptide Vaccine
  • Self-adjuvanting

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    Liu, T. Y., Hussein, W. M., Giddam, A. K., Jia, Z., Reiman, J. M., Zaman, M., McMillan, N. A. J., Good, M. F., Monteiro, M. J., Toth, I., & Skwarczynski, M. (2014). Polyacrylate-based delivery system for self-adjuvanting anticancer peptide vaccine. Journal of Medicinal Chemistry, 58(2), 888-896. https://doi.org/10.1021/jm501514h